(Hypertension. 2003;42:1075.)
© 2003 American Heart Association, Inc.
Brief Reviews |
From the Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Ga.
Correspondence to Kathy K. Griendling, Emory University, Division of Cardiology, 319 WMB, 1639 Pierce Drive, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
| Abstract |
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Key Words: antioxidants vascular disease muscle, smooth, vascular endothelium free radicals macrophages oxidative stress
| Introduction |
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| Reactive Oxygen Species |
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| Enzymatic Superoxide Production |
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NAD(P)H oxidases consist of multiple subunits: the electron transfer moieties (gp91phox, nox1 or nox4), p22phox, and regulatory subunits (p47phox, p67phox, and rac1). The expression pattern of these subunits varies among vascular cells.4 What makes the NAD(P)H oxidases so important in vascular function is their responsiveness to a variety of agonists, such as angiotensin (Ang) II.5 Enzyme activation occurs over the short term by stimulation of specific intracellular signals6 and over the long term by upregulation of the enzyme subunits.7,8 Even low Ang II concentrations (0.1 nmol/L) increase NAD(P)H oxidase-derived ROS, suggesting that this enzyme system is important physiologically.5
In certain circumstances, NOS can generate O2·- in addition to NO·. NOS utilizes L-arginine as a substrate to synthesize NO· in a tetrahydrobiopterin (H4B)-dependent manner. If the concentration of L-arginine or H4B is low, or if H4B is oxidized, NOS becomes uncoupled and generates significant amounts of O2·-.9 This occurs in hypertension, where activation of NAD(P)H oxidases leads to oxidation of H4B and production of large amounts of O2·- from endothelial NOS.10
Xanthine oxidoreductase is ubiquitous and appears in two interconvertible, yet functionally distinct, forms: xanthine dehydrogenase and XO.11 XO metabolizes hypoxanthine, xanthine, and NADH to form O2·- and H2O2. XO-generated ROS have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury, hypercholesterolemia and endothelial dysfunction in chronic heart failure.11,12
Recently, the role of MPO in vascular pathology has been highlighted. MPO is abundant in phagocytes and catalyzes H2O2 to produce HOCl and other oxidizing species.13 It also utilizes NO· to generate reactive nitrogen species, thereby reducing NO· bioactivity and increasing oxidative stress.14,15
| Effects of ROS on Vascular Cells |
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Impaired Endothelium-Dependent Vasorelaxation
In animal models, endothelial dysfunction occurs in association with increased ROS in numerous disease conditions,17 due to inactivation of NO· by O2·-. Importantly, SOD16 and probucol (a lipid-lowering drug with antioxidant potential)18 improve endothelium-dependent vasorelaxation in hypercholesterolemic animals. Endothelial dysfunction induced by Ang II infusion,19 deoxycorticosterone acetate (DOCA)-salt,20 or heart failure21 is reversed by SOD. Moreover, heterozygous deletion of GPx leads to impaired endothelium-dependent vasorelaxation.22 Because GPx is responsible for removal of peroxides, these data suggest that ROS other than O2·- also contribute to control of vasomotor function.
Apoptosis/Anoikis
Endothelial injury or exposure to O2·- and H2O2 induces apoptosis (programmed cell death) of ECs, which leads to EC loss and results in atherogenesis and a procoagulative state.23 Importantly, EC apoptosis stimulated by oxidized LDL, Ang II, high glucose, and TNF-
is inhibited by SOD, catalase, NAC, and antioxidant vitamins.23 These data strongly suggest that ROS regulate apoptotic mechanisms induced by a variety of stimuli. Another type of programmed cell death, anoikis, results from detachment of ECs from extracellular matrix. This process is also associated with increased intracellular ROS, probably from mitochondria, and is inhibited by NAC and diphenylene iodonium (DPI), a inhibitor of flavin-containing enzymes such as NAD(P)H oxidases.24
Expression of Adhesion Molecules
The endothelium normally presents an inert inflammatory surface. However, many proinflammatory stimuli induce the expression of adhesion molecules on ECs, leading to monocyte adhesion and ultimately atherosclerotic lesion formation. Expression of several adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), is ROS-dependent. Interleukin-1ß and TNF-
induced VCAM-1 gene expression is suppressed by the antioxidants pyrrolidine dithiocarbamate (PDTC) and NAC.25 Furthermore, NO·, which, because of its ability to scavenge radicals, can act as an antioxidant and reduces VCAM-1 expression stimulated by TNF-
, possibly by inhibiting the formation of peroxy-fatty acids.26 Induction of VCAM-1 and ICAM-1 expression by oscillatory shear stress is also inhibited by NAC.27 Taken together, these observations suggest that ROS promote adhesion of inflammatory cells.
Angiogenesis
Angiogenesis is important not only for physiological processes such as embryonic development and wound repair but also for pathological processes such as cancer, diabetic retinopathy, and atherosclerosis. EC migration, proliferation, and tube formation are essential events in the process of angiogenesis. ROS may be directly involved in all these mechanisms, as H2O2 has been shown to induce proliferation and migration of ECs and to mediate lymphocyte-activated tubulogenesis.28 ROS also act as mediators of angiogenic growth factors, such as vascular endothelial growth factor (VEGF).29 It has been reported that NAD(P)H oxidases regulate not only the induction of VEGF expression30 but also VEGF-induced angiogenesis.31
Vascular Smooth Muscle Cells
Many functions of VSMCs also depend on the production of ROS (Figure). Perhaps the most well-studied of these processes is cell growth, but ROS are also involved in migration as well as expression of inflammatory mediators and matrix components. In addition, ROS have been implicated in VSMC contraction.
VSMC Growth
Synthetic VSMCs, whose phenotype has been altered to support growth, are found in cardiovascular diseases such as hypertension, atherosclerosis, and restenosis after balloon angioplasty. ROS production is intimately involved in many of the processes leading to both hypertrophic and proliferative VSMC growth.
It has been known for many years that the vasoactive peptide Ang II can induce VSMC hypertrophy. This peptide was used to provide one of the first demonstrations that ROS are involved in the hypertrophic response. Ang IIinduced VSMC hypertrophy is inhibited by catalase and p22phox antisense,32,33 thus implicating NAD(P)H oxidase-derived ROS in the growth response.
ROS also mediate the full proliferative response to agonists such as PDGF and thrombin. H2O2 itself induces VSMC proliferation,34 although this effect is critically dependent on the concentration of H2O2 to which cells are exposed (see below). Furthermore, VSMC proliferation by PDGF or thrombin requires H2O2 generation, as it is inhibited by catalase, NAC, or DPI.35,36 Endogenously produced H2O2 may also be important in modulating survival and proliferation of VSMCs, because overexpression of catalase inhibits basal smooth muscle proliferation while increasing the rate of apoptosis.37
Although the effects of ROS described above are positive for VSMC growth, ROS induce VSMC apoptosis and differentiation as well. Li et al38 showed that exposure of VSMCs to glucose/glucose oxidase or diethylmaleate induces apoptosis through the formation of hydroxyl radicals, whereas Su et al39 reported that endogenous ROS can increase VSMC maturation and differentiation. These apparent paradoxical effects may be explained by the identity and amount of ROS to which VSMCs are exposed. High concentrations of H2O2 (500 µmol/L to 1 mmol/L) induce apoptosis, whereas moderate concentrations (100 µmol/L) cause cell cycle arrest in G1.40
Migration
VSMC migration is considered to be one of the major components of vascular pathogenesis. Although the precise molecular mechanisms of VSMC migration are unclear, a role for ROS has clearly been demonstrated. Sundaresan et al35 showed that PDGF-induced VSMC chemotaxis is inhibited by catalase overexpression. This has recently been confirmed by Weber et al,41 who demonstrated that VSMC migration stimulated by PDGF is inhibited by NAC, DPI, ebselen, and dominant-negative Rac, suggesting that O2·- production through the NAD(P)H oxidase is critical for agonist-stimulated VSMC migration. It will be of great interest to identify the cadre of signaling molecules that are responsible for ROS-dependent VSMC migration.
Matrix Regulation
Degradation and reorganization of the extracellular matrix by matrix metalloproteinases (MMPs) are prominent events in physiological and pathological vascular remodeling. Recent studies have revealed that activity of MMPs can be modulated by ROS. Rajagopalan et al42 demonstrated that proMMP-2 and proMMP-9 secreted from human VSMCs are activated by ROS. Insight into the mechanism by which ROS regulate MMP activity was provided by Fu et al,43 who found MPO-derived HOCl activates MMP-7 by oxygenation of the cysteine residue, which is a mechanism distinct from the well-known proteolytic cleavage of MMP proenzyme. Gene expression of MMPs can also be regulated by ROS. In VSMCs exposed to mechanical stretch, MMP-2 mRNA is increased in an NAD(P)H oxidase-derived, ROS-sensitive manner.44 Thus, ROS modulate matrix remodeling at multiple levels.
Inflammatory Gene Expression
It has been recognized that atherosclerosis is an inflammatory disease in which various cytokines play a significant role in the progression of vascular lesions. One of the major mechanisms by which cytokine gene expression is increased is the activation of nuclear factor-
B (NF-
B). NF-
B is a ROS-sensitive transcription factor and has a central role in the expression of proinflammatory genes, including monocyte chemotactic protein-1 (MCP-1) and interleukin-6.45 In VSMCs, Ang II and TNF-
were shown to induce these genes through the activation of NF-
B in a ROS-dependent manner.4648
Contraction
As discussed above, it is well established that O2·- regulates vasomotor tone through the inactivation of NO·. However, the direct effect of ROS on VSMC is controversial. H2O2 induces vasorelaxation of pulmonary,49 coronary,50 and mesenteric arteries.51 In contrast, ROS generated by XO are vasoconstrictive in aorta, and ROS-induced contraction is augmented in spontaneously hypertensive rats (SHR).52 Furthermore, contraction of aorta to Ang II is inhibited by catalase.53 These apparent discrepancies may be due to the vascular bed studied or the concentration of ROS generated in the particular system. Further work is necessary to fully elucidate the effects of ROS on contraction.
| Clinical Implications |
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Atherosclerotic lesions in human coronary arteries show intense expression of gp91phox in the vulnerable shoulder region of the plaque, coincident with macrophage localization.54 In addition, nox4 is upregulated during the atheroma phase of lesion formation but is reduced in advanced lesions.54 The functional significance of these enzyme systems was confirmed by animal experiments. Genetic deletion of p47phox in ApoE knockout mice (ApoE-/-, a model of atherosclerosis), results in reduction of lesion area in the descending aorta compared with that in ApoE-/- mice.55 This study indicates that NAD(P)H oxidasederived ROS generation has a requisite role in atherosclerotic lesion formation.
Less is known about the role of XO and MPO in atherosclerosis. In hypercholesterolemic rabbit aorta56 and human atherosclerotic coronary artery,57 a role for XO-derived ROS in impaired endothelium-dependent vasorelaxation was reported. Furthermore, XO is present at high concentrations in atherosclerotic plaques.58 In human subjects, there is a remarkable association between blood MPO levels and risk of coronary disease,59 and atherosclerotic coronary arteries have higher levels of proteins oxidized by MPO-derived HOCl than do normal coronary arteries.60 However, transplantation of bone marrow cells derived from MPO-deficient mice into LDL receptordeficient mice results in accelerated atherosclerosis, suggesting a protective role for MPO in the progression of atherosclerosis.61 Further investigations are needed to define the cause-effect relation between XO, MPO, and atherosclerosis.
One of the defining features of atherosclerosis is the episodic nature of lesion development. Hemodynamic influences are proposed to be responsible for the discontinuous nature of plaque formation because lesions tend to form in regions of disturbed flow.62 Whereas introduction of laminar shear stress presents a transient prooxidant signal that is quickly corrected by upregulation of antioxidant enzymes, oscillatory shear stress activates both NAD(P)H oxidases and XO in the absence of a compensatory upregulation of SOD.63,64 Based on the known effects of ROS on endothelial function (see above), these data suggest that ROS produced by disturbed flow may be one mechanism by which these areas are predisposed to lesion formation.
Hypertension
A number of studies have suggested that oxidative stress is deeply involved in the pathogenesis of hypertension.6 These effects are mediated by inactivation of NO· by O2·- in the vasculature and the kidney, and by H2O2-induced vessel remodeling. Vaziri et al65 showed that induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Furthermore, Ang IIinduced O2·- production and hypertension are markedly blunted in mice lacking the p47phox subunit of NAD(P)H oxidase.66 Renovascular hypertension (RVH), an Ang IIdependent form of hypertension, is accompanied by increased oxidative stress in animal models67 and human subjects.68 The cell-permeable SOD mimetic tempol lowers blood pressure in the 1-kidney, 1-clip model of RVH69 Oxidative stress plays a role in low renin hypertension as well. In the DOCA-salt hypertension model, vascular production of O2·- is increased in association with upregulation of p22phox,70 and long-term treatment with tempol lowers blood pressure.71 Finally, in the SHR, blood pressure can be lowered with PEG-SOD,72 tempol,73 or an antioxidant-rich diet.74
When investigating the role of oxidative stress in models of vascular disease, the effect of the intervention on both the enzymes that produce ROS and those responsible for their removal must be considered. For example, Ang II not only increases NAD(P)H oxidase activity but also upregulates ecSOD, possibly to compensate for the increased ROS.75 In situations where this compensatory effect is efficient, ROS levels may appear normal even in the face of prooxidant stresses such as Ang II. In Dahl salt-resistant rats on a low salt diet, Ang II levels are high but O2·- is actually decreased, perhaps because of the accompanying increase in MnSOD expression.76 This ability to increase antioxidant defenses may be sufficient to protect the vasculature from low levels of oxidant stress, allowing ROS to function as signaling molecules. However, when ROS production becomes overwhelming, compensatory mechanisms are inadequate and pathophysiological consequences ensue.
Diabetes Mellitus
Cardiovascular complications are the leading cause of morbidity and mortality in patients with diabetes mellitus (DM). Evidence implicating ROS in the development of diabetic vascular dysfunction has been expanding rapidly in recent years. Hyperglycemia and increased free fatty acids in the bloodstream, the chief characteristics of DM, can both lead to leakage of O2·- from the mitochondrial respiration process and NAD(P)H oxidase activation.77 Furthermore, saphenous veins and internal mammary arteries from diabetic patients have increased NAD(P)H oxidase activity and uncoupling of eNOS compared with that in matched control subjects.78 Increased production of ROS, in turn, leads to impaired endothelium-dependent vasorelaxation in models of both type 1 and type 2 DM.79,80 The relation between ROS and the vascular complications of DM is discussed more fully in a recent review.81
Restenosis After Angioplasty
Restenosis is a frequent complication of balloon angioplasty. In this pathological process, VSMCs undergo apoptosis, proliferation, and migration. Adventitial fibroblasts also participate in lesion formation by differentiating into myofibroblasts and migrating to the neointima.82 As discussed above, ROS are able to induce these phenotypic changes, suggesting that they may contribute to the pathogenesis of restenosis in vivo.
Superoxide production is increased after balloon injury, especially in medial and neointimal smooth muscle cells and adventitial fibroblasts.83 ROS appear to be functionally important, because neointima formation is inhibited by antioxidants.83 Although the oxidase(s) responsible for the production of ROS after balloon injury have not been fully identified, a role for NAD(P)H oxidases has been reported. DPI abolishes O2·- generation in porcine coronary arteries.84 Subunits of the enzyme, including p47phox, nox1, nox4, gp91phox, and p22phox, are upregulated after injury.36,85 Very recently, Jacobson et al86 reported that a specific peptide inhibitor for NAD(P)H oxidases inhibited restenosis, suggesting a mechanistic role for these enzymes in restenosis.
| Controversy in Clinical Trials |
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| Acknowledgments |
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Received July 25, 2003; first decision August 14, 2003; accepted September 30, 2003.
| References |
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2. Droge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002; 82: 4795.
3. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000; 86: 494501.
4. Hanna IR, Taniyama Y, Szocs K, Rocic P, Griendling KK. NAD(P)H oxidase-derived reactive oxygen species as mediators of angiotensin II signaling. Antioxid Redox Signal. 2002; 4: 899914.[CrossRef][Medline] [Order article via Infotrieve]
5. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res. 1994; 74: 11411148.
6. Lassègue B, Clempus RE. Vascular NAD (P)H oxidase: specific features, expression and regulation. Am J Physiol Endocrinol Metab. 2003; 285: R277R297.
7. Lassègue B, Sorescu D, Szöcs K, Yin Q, Akers M, Zhang Y, Grant SL, Lambeth JD, Griendling KK. Novel gp91phox homologues in vascular smooth muscle cells: nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res. 2001; 88: 888894.
8. Touyz RM, Chen X, Tabet F, Yao G, He G, Quinn MT, Pagano PJ, Schiffrin EL. Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Circ Res. 2002; 90: 12051213.
9. Stuehr D, Pou S, Rosen GM. Oxygen reduction by nitric-oxide synthases. J Biol Chem. 2001; 276: 1453314536.
10. Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, Mitch WE, Harrison DG. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003; 111: 12011209.[CrossRef][Medline] [Order article via Infotrieve]
11. Harrison R. Structure and function of xanthine oxidoreductase: where are we now? Free Radic Biol Med. 2002; 33: 774797.[CrossRef][Medline] [Order article via Infotrieve]
12. Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C, Harrison DG, Hornig B, Drexler H. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine-oxidase and extracellular superoxide dismutase. Circulation. 2002; 106: 30733078.
13. Winterbourn CC, Vissers MC, Kettle AJ. Myeloperoxidase. Curr Opin Hematol. 2000; 7: 5358.[CrossRef][Medline] [Order article via Infotrieve]
14. Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA. Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science. 2002; 296: 23912394.
15. Gaut JP, Byun J, Tran HD, Lauber WM, Carroll JA, Hotchkiss RS, Belaaouaj A, Heinecke JW. Myeloperoxidase produces nitrating oxidants in vivo. J Clin Invest. 2002; 109: 13111319.[CrossRef][Medline] [Order article via Infotrieve]
16. Mugge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG. Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res. 1991; 69: 12931300.
17. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000; 87: 840844.
18. Keaney JF Jr, Xu A, Cunningham D, Jackson T, Frei B, Vita JA. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest. 1995; 95: 25202529.[Medline] [Order article via Infotrieve]
19. Laursen JB, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG. Role of superoxide in angiotensin IIinduced but not catecholamine-induced hypertension. Circulation. 1997; 95: 588593.
20. Somers MJ, Mavromatis K, Galis ZS, Harrison DG. Vascular superoxide production and vasomotor function in hypertension induced by deoxycorticosterone acetate-salt. Circulation. 2000; 101: 17221728.
21. Bauersachs J, Bouloumie A, Fraccarollo D, Hu K, Busse R, Ertl G. Endothelial dysfunction in chronic myocardial infarction despite increased vascular endothelial nitric oxide synthase and soluble guanylate cyclase expression: role of enhanced vascular superoxide production. Circulation. 1999; 100: 292298.
22. Forgione MA, Cap A, Liao R, Moldovan NI, Eberhardt RT, Lim CC, Jones J, Goldschmidt-Clermont PJ, Loscalzo J. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure. Circulation. 2002; 106: 11541158.
23. Dimmeler S, Zeiher AM. Reactive oxygen species and vascular cell apoptosis in response to angiotensin II and pro-atherosclerotic factors. Regul Pept. 2000; 90: 1925.[CrossRef][Medline] [Order article via Infotrieve]
24. Li AE, Ito H, Rovira II, Kim KS, Takeda K, Yu ZY, Ferrans VJ, Finkel T. A role for reactive oxygen species in endothelial cell anoikis. Circ Res. 1999; 85: 304310.
25. Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, Alexander RW, Medford RM. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993; 92: 18661874.[Medline] [Order article via Infotrieve]
26. Khan BV, Harrison DG, Olbrych MT, Alexander RW, Medford RM. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci U S A. 1996; 93: 91149119.
27. Chappell DC, Varner SE, Nerem RM, Medford RM, Alexander RW. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res. 1998; 82: 532539.
28. Maulik N, Das DK. Redox signaling in vascular angiogenesis. Free Radic Biol Med. 2002; 33: 10471060.[CrossRef][Medline] [Order article via Infotrieve]
29. Kuroki M, Voest EE, Amano S, Beerepoot LV, Takashima S, Tolentino M, Kim RY, Rohan RM, Colby KA, Yeo KT, Adamis AP. Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo. J Clin Invest. 1996; 98: 16671675.[Medline] [Order article via Infotrieve]
30. Arbiser JL, Petros J, Klafter R, Govindajaran B, McLaughlin ER, Brown LF, Cohen C, Moses M, Kilroy S, Arnold RS, Lambeth JD. Reactive oxygen generated by Nox1 triggers the angiogenic switch. Proc Natl Acad Sci U S A. 2002; 99: 715720.
31. Ushio-Fukai M, Tang Y, Fukai T, Dikalov SI, Ma Y, Fujimoto M, Quinn MT, Pagano PJ, Johnson C, Alexander RW. Novel role of gp91(phox)-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ Res. 2002; 91: 11601167.
32. Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem. 1996; 271: 2331723321.
33. Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, Taylor WR, Griendling KK. Role of NADH/NADPH oxidase-derived H2O2 in angiotensin IIinduced vascular hypertrophy. Hypertension. 1998; 32: 488495.
34. Rao GN, Berk BC. Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. Circ Res. 1992; 70: 593599.
35. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 1995; 270: 296299.
36. Patterson C, Ruef J, Madamanchi NR, Barry-Lane P, Hu Z, Horaist C, Ballinger CA, Brasier AR, Bode C, Runge MS. Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin: evidence that p47(phox) may participate in forming this oxidase in vitro and in vivo. J Biol Chem. 1999; 274: 1981419822.
37. Brown MR, Miller FJ Jr, Li WG, Ellingson AN, Mozena JD, Chatterjee P, Engelhardt JF, Zwacka RM, Oberley LW, Fang X, Spector AA, Weintraub NL. Overexpression of human catalase inhibits proliferation and promotes apoptosis in vascular smooth muscle cells. Circ Res. 1999; 85: 524533.
38. Li PF, Dietz R, von Harsdorf R. Reactive oxygen species induce apoptosis of vascular smooth muscle cell. FEBS Lett. 1997; 404: 249252.[CrossRef][Medline] [Order article via Infotrieve]
39. Su B, Mitra S, Gregg H, Flavahan S, Chotani MA, Clark KR, Goldschmidt-Clermont PJ, Flavahan NA. Redox regulation of vascular smooth muscle cell differentiation. Circ Res. 2001; 89: 3946.
40. Deshpande NN, Sorescu D, Seshiah P, Ushio-Fukai M, Akers M, Yin Q, Griendling KK. Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle. Antioxid Redox Signal. 2002; 4: 845854.[CrossRef][Medline] [Order article via Infotrieve]
41. Weber DS, Seshiah P, Taniyama Y, Griendling KK. Src-dependent migration of vascular smooth muscle cells by PDGF is reactive oxygen species dependent. Circulation. 2002; 106 (suppl II): II260.Abstract.
42. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 1996; 98: 25722579.[Medline] [Order article via Infotrieve]
43. Fu X, Kassim SY, Parks WC, Heinecke JW. Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7): a mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem. 2001; 276: 4127941287.
44. Grote K, Flach I, Luchtefeld M, Akin E, Holland SM, Drexler H, Schieffer B. Mechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen species. Circ Res. 2003; 92: e80e86.[CrossRef][Medline] [Order article via Infotrieve]
45. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002; 2: 725734.[CrossRef][Medline] [Order article via Infotrieve]
46. Chen XL, Tummala PE, Olbrych MT, Alexander RW, Medford RM. Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. Circ Res. 1998; 83: 952959.
47. Han Y, Runge MS, Brasier AR. Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcription factors. Circ Res. 1999; 84: 695703.
48. De Keulenaer GW, Ushio-Fukai M, Yin Q, Chung AB, Lyons PR, Ishizaka N, Rengarajan K, Taylor WR, Alexander RW, Griendling KK. Convergence of redox-sensitive and mitogen-activated protein kinase signaling pathways in tumor necrosis factor-alpha-mediated monocyte chemoattractant protein-1 induction in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2000; 20: 385391.
49. Burke TM, Wolin MS. Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation. Am J Physiol. 1987; 252: H721H732.[Medline] [Order article via Infotrieve]
50. Iesaki T, Gupte SA, Kaminski PM, Wolin MS. Inhibition of guanylate cyclase stimulation by NO and bovine arterial relaxation to peroxynitrite and H2O2. Am J Physiol. 1999; 277: H978H985.[Medline] [Order article via Infotrieve]
51. Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, Takeshita A. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest. 2000; 106: 15211530.[Medline] [Order article via Infotrieve]
52. Auch-Schwelk W, Katusic ZS, Vanhoutte PM. Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension. 1989; 13: 859864.
53. Torrecillas G, Boyano-Adanez MC, Medina J, Parra T, Griera M, Lopez-Ongil S, Arilla E, Rodriguez-Puyol M, Rodriguez-Puyol D. The role of hydrogen peroxide in the contractile response to angiotensin II. Mol Pharmacol. 2001; 59: 104112.
54. Sorescu D, Weiss D, Lassegue B, Clempus RE, Szocs K, Sorescu GP, Valppu L, Quinn MT, Lambeth JD, Vega JD, Taylor WR, Griendling KK. Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation. 2002; 105: 14291435.
55. Barry-Lane PA, Patterson C, van der Merwe M, Hu Z, Holland SM, Yeh ET, Runge MS. p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice. J Clin Invest. 2001; 108: 15131522.[CrossRef][Medline] [Order article via Infotrieve]
56. White CR, Darley-Usmar V, Berrington WR, McAdams M, Gore JZ, Thompson JA, Parks DA, Tarpey MM, Freeman BA. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci U S A. 1996; 93: 87458749.
57. Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, Reepschlager N, Hornig B, Drexler H, Harrison DG. Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation. 2003; 107: 13831389.
58. Patetsios P, Song M, Shutze WP, Pappas C, Rodino W, Ramirez JA, Panetta TF. Identification of uric acid and xanthine oxidase in atherosclerotic plaque. Am J Cardiol. 2001; 88: 188191.[CrossRef][Medline] [Order article via Infotrieve]
59. Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, Topol EJ, Sprecher DL, Hazen SL. Association between myeloperoxidase levels and risk of coronary artery disease. JAMA. 2001; 286: 21362142.
60. Woods AA, Linton SM, Davies MJ. Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques. Biochem J. 2003; 370: 729735.[CrossRef][Medline] [Order article via Infotrieve]
61. Brennan ML, Anderson MM, Shih DM, Qu XD, Wang X, Mehta AC, Lim LL, Shi W, Hazen SL, Jacob JS, Crowley JR, Heinecke JW, Lusis AJ. Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest. 2001; 107: 419430.[Medline] [Order article via Infotrieve]
62. Ku D, Giddens D, Zarins C, Glagov S. Pulsatile flow and atherosclerosis in the human carotid bifurcation: positive correlation between plaque location and low and oscillating shear stress. Arteriosclerosis. 1985; 5: 293302.
63. De Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK. Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res. 1998; 82: 10941101.
64. McNally JS, Davis ME, Giddens DP, Saha A, Hwang J, Dikalov S, Jo H, Harrison DG. Role of xanthine oxidoreductase and the NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol. 2003; September 4 (Epub ahead of print).
65. Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension. 2000; 36: 142146.
66. Landmesser U, Cai H, Dikalov S, McCann L, Hwang J, Jo H, Holland SM, Harrison DG. Role of p47(phox) in vascular oxidative stress and hypertension caused by angiotensin II. Hypertension. 2002; 40: 511515.
67. Heitzer T, Wenzel U, Hink U, Krollner D, Skatchkov M, Stahl RA, MacHarzina R, Brasen JH, Meinertz T, Munzel T. Increased NAD(P)H oxidase-mediated superoxide production in renovascular hypertension: evidence for an involvement of protein kinase C. Kidney Int. 1999; 55: 252260.[CrossRef][Medline] [Order article via Infotrieve]
68. Minuz P, Patrignani P, Gaino S, Degan M, Menapace L, Tommasoli R, Seta F, Capone ML, Tacconelli S, Palatresi S, Bencini C, Del Vecchio C, Mansueto G, Arosio E, Santonastaso CL, Lechi A, Morganti A, Patrono C. Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease. Circulation. 2002; 106: 28002805.
69. Dobrian AD, Schriver SD, Prewitt RL. Role of angiotensin II and free radicals in blood pressure regulation in a rat model of renal hypertension. Hypertension. 2001; 38: 361366.
70. Beswick RA, Dorrance AM, Leite R, Webb RC. NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. Hypertension. 2001; 38: 11071111.
71. Beswick RA, Zhang H, Marable D, Catravas JD, Hill WD, Webb RC. Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response. Hypertension. 2001; 37: 781786.
72. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A. 1991; 88: 1004510048.
73. Schnackenberg CG, Welch WJ, Wilcox CS. Normalization of blood pressure and renal vascular resistance in SHR with a membrane-permeable superoxide dismutase mimetic: role of nitric oxide. Hypertension. 1998; 32: 5964.
74. Rodriguez-Iturbe B, Zhan CD, Quiroz Y, Sindhu RK, Vaziri ND. Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats. Hypertension. 2003; 41: 341346.
75. Fukai T, Siegfried MR, Ushio-Fukai M, Griendling KK, Harrison DG. Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res. 1999; 85: 2328.
76. Meng S, Roberts LJ II, Cason GW, Curry TS, Manning RD Jr. Superoxide dismutase and oxidative stress in Dahl salt-sensitive and -resistant rats. Am J Physiol Regul Integr Comp Physiol. 2002; 283: R732R738.
77. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev. 2002; 23: 599622.
78. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, Channon KM. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation. 2002; 105: 16561662.
79. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, Skatchkov M, Thaiss F, Stahl RA, Warnholtz A, Meinertz T, Griendling K, Harrison DG, Forstermann U, Munzel T. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001; 88: E14E22.[Medline] [Order article via Infotrieve]
80. Kim YK, Lee MS, Son SM, Kim IJ, Lee WS, Rhim BY, Hong KW, Kim CD. Vascular NADH oxidase is involved in impaired endothelium-dependent vasodilation in OLETF rats, a model of type 2 diabetes. Diabetes. 2002; 51: 522527.
81. Spitaler MM, Graier WF. Vascular targets of redox signalling in diabetes mellitus. Diabetologia. 2002; 45: 476494.[CrossRef][Medline] [Order article via Infotrieve]
82. Wilcox JN, Cipolla GD, Martin FH, Simonet L, Dunn B, Ross CE, Scott NA. Contribution of adventitial myofibroblasts to vascular remodeling and lesion formation after experimental angioplasty in pig coronary arteries. Ann N Y Acad Sci. 1997; 811: 437447.[Medline] [Order article via Infotrieve]
83. Azevedo LC, Pedro MA, Souza LC, de Souza HP, Janiszewski M, da Luz PL, Laurindo FR. Oxidative stress as a signaling mechanism of the vascular response to injury: the redox hypothesis of restenosis. Cardiovasc Res. 2000; 47: 436445.
84. Shi Y, Niculescu R, Wang D, Patel S, Davenpeck KL, Zalewski A. Increased NAD(P)H oxidase and reactive oxygen species in coronary arteries after balloon injury. Arterioscler Thromb Vasc Biol. 2001; 21: 739745.
85. Szöcs K, Lassegue B, Sorescu D, Hilenski LL, Valppu L, Couse TL, Wilcox JN, Quinn MT, Lambeth JD, Griendling KK. Upregulation of Nox-based NAD(P)H oxidases in restenosis after carotid injury. Arterioscler Thromb Vasc Biol. 2002; 22: 2127.
86. Jacobson GM, Dourron HM, Liu J, Carretero OA, Reddy DJ, Andrzejewski T, Pagano PJ. Novel NAD (P)H oxidase inhibitor suppresses angioplasty-induced superoxide and neointimal hyperplasia of rat carotid artery. Circ Res. 2003; 92: 637643.
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H. Cai NAD(P)H Oxidase-Dependent Self-Propagation of Hydrogen Peroxide and Vascular Disease Circ. Res., April 29, 2005; 96(8): 818 - 822. [Abstract] [Full Text] [PDF] |
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P. K. Aley, K. E. Porter, J. P. Boyle, P. J. Kemp, and C. Peers Hypoxic Modulation of Ca2+ Signaling in Human Venous Endothelial Cells: MULTIPLE ROLES FOR REACTIVE OXYGEN SPECIES J. Biol. Chem., April 8, 2005; 280(14): 13349 - 13354. [Abstract] [Full Text] [PDF] |
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A. Ergul, J. S. Johansen, C. Stromhaug, A. K. Harris, J. Hutchinson, A. Tawfik, A. Rahimi, E. Rhim, B. Wells, R. W. Caldwell, et al. Vascular Dysfunction of Venous Bypass Conduits Is Mediated by Reactive Oxygen Species in Diabetes: Role of Endothelin-1 J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 70 - 77. [Abstract] [Full Text] [PDF] |
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D. M. Pollock Endothelin, Angiotensin, and Oxidative Stress in Hypertension Hypertension, April 1, 2005; 45(4): 477 - 480. [Full Text] [PDF] |
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M. Tsuda, M. Iwai, J.-M. Li, H.-S. Li, L.-J. Min, A. Ide, M. Okumura, J. Suzuki, M. Mogi, H. Suzuki, et al. Inhibitory Effects of AT1 Receptor Blocker, Olmesartan, and Estrogen on Atherosclerosis Via Anti-Oxidative Stress Hypertension, April 1, 2005; 45(4): 545 - 551. [Abstract] [Full Text] [PDF] |
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R. A. Kowluru and S. Odenbach Role of Interleukin-1{beta} in the Development of Retinopathy in Rats: Effect of Antioxidants Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 4161 - 4166. [Abstract] [Full Text] [PDF] |
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S. Sela, R. Mazor, M. Amsalam, C. Yagil, Y. Yagil, and B. Kristal Primed Polymorphonuclear Leukocytes, Oxidative Stress, and Inflammation Antecede Hypertension in the Sabra Rat Hypertension, November 1, 2004; 44(5): 764 - 769. [Abstract] [Full Text] [PDF] |
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Md. R. Abid, I. G. Schoots, K. C. Spokes, S.-Q. Wu, C. Mawhinney, and W. C. Aird Vascular Endothelial Growth Factor-mediated Induction of Manganese Superoxide Dismutase Occurs through Redox-dependent Regulation of Forkhead and I{kappa}B/NF-{kappa}B J. Biol. Chem., October 15, 2004; 279(42): 44030 - 44038. [Abstract] [Full Text] [PDF] |
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S. Chatterjee and A. B. Fisher ROS to the rescue Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L704 - L705. [Full Text] [PDF] |
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L. C. Santarelli, J. Chen, S. H. Heinemann, and T. Hoshi The {beta}1 Subunit Enhances Oxidative Regulation of Large-Conductance Calcium-activated K+ Channels J. Gen. Physiol., September 27, 2004; 124(4): 357 - 370. [Abstract] [Full Text] [PDF] |
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R. M. Touyz Reactive Oxygen Species, Vascular Oxidative Stress, and Redox Signaling in Hypertension: What Is the Clinical Significance? Hypertension, September 1, 2004; 44(3): 248 - 252. [Abstract] [Full Text] [PDF] |
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D. H. Endemann and E. L. Schiffrin Endothelial Dysfunction J. Am. Soc. Nephrol., August 1, 2004; 15(8): 1983 - 1992. [Abstract] [Full Text] [PDF] |
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E. L. Schiffrin and R. M. Touyz From bedside to bench to bedside: role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H435 - H446. [Full Text] [PDF] |
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G. S. Jose, M. U. Moreno, S. Olivan, O. Beloqui, A. Fortuno, J. Diez, and G. Zalba Functional Effect of the p22phox -930A/G Polymorphism on p22phox Expression and NADPH Oxidase Activity in Hypertension Hypertension, August 1, 2004; 44(2): 163 - 169. [Abstract] [Full Text] [PDF] |
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G. Wang, J. Anrather, J. Huang, R. C. Speth, V. M. Pickel, and C. Iadecola NADPH Oxidase Contributes to Angiotensin II Signaling in the Nucleus Tractus Solitarius J. Neurosci., June 16, 2004; 24(24): 5516 - 5524. [Abstract] [Full Text] [PDF] |
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G. Ceolotto, M. Bevilacqua, I. Papparella, E. Baritono, L. Franco, C. Corvaja, M. Mazzoni, A. Semplicini, and A. Avogaro Insulin Generates Free Radicals by an NAD(P)H, Phosphatidylinositol 3'-Kinase-Dependent Mechanism in Human Skin Fibroblasts Ex Vivo Diabetes, May 1, 2004; 53(5): 1344 - 1351. [Abstract] [Full Text] [PDF] |
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M. S. Wolin Subcellular Localization of Nox-Containing Oxidases Provides Unique Insight Into Their Role in Vascular Oxidant Signaling Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 625 - 627. [Full Text] [PDF] |
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