Published online before print April 21, 2008, doi: 10.1161/HYPERTENSIONAHA.107.109066
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2008;51:1537.)
© 2008 American Heart Association, Inc.
Original Articles |
Hypertension Impairs Postnatal Vasculogenesis
Role of Antihypertensive Agents
From the Cardiovascular Research Center INSERM U689 Lariboisière (D.Y., C.C., C.L., J.V., M.D., B.I.L., J.-S.S.), Université Paris 7, Hôpital Lariboisière, Paris, France; and the Department of Cell Biology & Genetics/Vascular Surgery (B.M.), Erasmus University Medical Center, Rotterdam, The Netherlands.
Correspondence to Jean-Sebastien Silvestre, INSERM U689, Hopital Lariboisière, 41 bvd de la chapelle, 75475 Paris Cedex 10, France. E-mail Jean-Sebastien.Silvestre{at}larib.inserm.fr
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
We analyzed the effect of hypertension on postischemic vasculogenesis. Ischemia was induced by right femoral artery ligature in Wistar Kyoto rats (WKY) or spontaneously hypertensive rats (SHR) treated with or without angiotensin-converting enzyme inhibitor (Perindopril, 0.76 mg/kg/d) and angiotensin type 1 receptor blocker (losartan, 30 mg/kg/d). Basal postischemic neovascularization was reduced in SHR compared to WKY (P<0.05, n=8). Treatment with ACE inhibitor or angiotensin type 1 receptor blocker decreased blood pressure levels by 1.4- and 1.3-fold (P<0.001), respectively and restored vessel growth in SHR to WKY levels. Interestingly, 14 days after bone-marrow mononuclear cell (BM-MNC) transfusion, angiographic scores, capillary density, and foot perfusion were decreased by 1.4-, 1.5-, and 1.2-fold, respectively in SHR transfused with BM-MNCs isolated from SHR compared to those receiving BM-MNCs of WKY (P<0.05, n=6). Alteration in BM-MNCs proangiogenic potential was likely related to the reduction in their ability to mobilize into peripheral circulation, as revealed by the 2.9-fold decrease in number of circulating CD34+/CD117+ cells (P<0.001) and to differentiate into cells with endothelial phenotype, as revealed by the 2.1-fold reduction in percentages of DilLDL/BS-1 lectin positive cells (P<0.001). In addition, reactive oxygen species (ROS) levels were increased by 2.2-fold in SHR BM-MNCs compared to WKY BM-MNCs (P<0.01), as assessed by L-012 luminescence. Cotreatment with ACE inhibitor, angiotensin type 1 receptor blocker, or antioxidants (NAC 3 mmol/L, Apocynin 200 µmol/L) reduced ROS levels, improved the number of DilLDL/BS-1 lectin-positive cells by around 1.5-fold, and restored BM-MNCs proangiogenic effects in ischemic hindlimb. In conclusion, alteration in progenitor cell proangiogenic function may participate to the hypertension-induced impairment in postischemic revascularization.
Key Words: hypertension • angiogenesis • progenitor cells • angiotensin converting enzyme • angiotensin type I receptor
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The revascularization process, including vasculogenesis, angiogenesis, and collateral growth, characterizes tissue repair and remodeling occurring in acute and chronic ischemic vascular diseases. In particular, postnatal vasculogenesis referred to the homing and differentiation of circulating progenitor cells from bone marrow or non–bone marrow origins1 into endothelial cells within sites of active neovascularization. In addition, circulating progenitor cells may deliver angiogenic growth factors to pathological tissues and contribute to neovascularization and tissue/vessel remodeling by paracrine effects.2,3
In most clinical settings, however, these natural adaptive responses to a compromised perfusion are insufficient to block the progression of ischemic diseases. Hence, certain cardiovascular risk factors including diabetes, aging, and hypercholesterolemia adversely affect postnatal vasculogenesis and revascularization in animals models of limb ischemia.4–7 In support of this view, patients with type I and II diabetes displayed a reduction in endothelial progenitor cell (EPC) number and angiogenicity.8,9
In most forms of clinical and experimental hypertension, increased arterial blood pressure is associated with microvascular rarefaction and increased peripheral vascular resistances.10 Similarly, postischemic reparative neovascularization is impaired in spontaneously hypertensive rats (SHR) as a function of progression of the hypertensive disease.11,12 Several molecular and cellular mechanisms may be involved in the hypertension-induced impairment in vessel growth. First, the angiogenic capacity of serum derived from SHR was less than that from normotensive animals in a chick embryo chorio-allantoic membrane model.13 Protein levels of key proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor are also reduced in hypertensive animals.11,14 Second, previous observations that endothelial function is impaired in SHR as well as in patients with essential hypertension imply that the defective endothelial function may contribute to impaired angiogenesis in SHR.15,16,17 Alternatively, the participation of progenitor cell dysfunction to the pathogenesis of hypertension can be speculated. In adult subjects without history of cardiovascular diseases, the number of circulating EPCs was inversely correlated with the endothelial function and the Framingham risk score, which includes systolic blood pressure as a major component.18 Recently, accelerated senescence of EPCs was demonstrated in hypertensive animals and humans.19
We therefore hypothesized that hypertension may decrease bone marrow–derived mononuclear cell (BM-MNC) number and proangiogenic potential leading to abrogation in postischemic revascularization. We provide evidence that hypertension reduces circulating progenitor cells number and ability to differentiate into endothelial cells. Furthermore, we find that antihypertensive treatments using either an angiotensin converting enzyme (ACE) inhibitor (perindopril), an angiotensin II type I receptor (AT1R) blocker (losartan), or a nonspecific vasodilator hydralazine could restore BM-MNC dysfunction by blocking the hypertension-induced oxidative stress.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Animal Model
Twelve-week-old male normotensive Wistar Kyoto rats (WKY) and SHR were separated into 8 groups (n=6 to 8) receiving the following treatment for 3 weeks in drinking water: placebo, ACE inhibitor (perindopril, 0.76 mg/kg per day, Servier), AT1R blocker (losartan, 30 mg/kg per day, MSD-Chibret), and hydralazine (hydralazine hydrochloride, 200 mg/L, drinking water, Sigma). Untreated WKY and SHR served as control groups. All the experiments were performed in accordance with the European Community guidelines for the care and use of laboratory animals (No. 07430).
Arterial Pressure Measurement
Systolic blood pressure was measured in conscious rats, by the tail-cuff method, between 9 AM and 12 AM (BP2000, Visitech system). Blood pressure was measured for 10 different consecutive cycles.
Ischemic Hindlimb Model
After 1 week of treatment, rats were anesthetized and right femoral artery was occluded (6-0 silk suture) by ligature. The ligature was performed on the femoral artery 0.5 cm proximal to the bifurcation of the saphenous and popliteal arteries, as previously described.20 After 2 weeks of ischemia, vessel density was determined by high-definition microangiography and capillary density analysis in hindlimb. Laser-doppler perfusion imaging was also used to assess in vivo tissue perfusion in the paw, as previously described.3,20
BM-MNC Isolation
Bone marrow was obtained by flushing tibia and femur, low-density mononuclear cells were then isolated by centrifugation on a Ficoll gradient, as previously described.3,4 Alternatively, 5 mL of blood was collected in EDTA-containing tubes. After centrifugation on a Ficoll gradient and red cell lysis, circulating blood mononuclear cells were then analyzed in flow analysis cytometry system (FACS).
Flow Analysis Cytometry System (FACS) Analysis
106 BM-MNCs or circulating MNCs were incubated for 15 minutes at 4°C with 5% SVF fetal bovine serum and then with 20 µL of fluorescein (FITC)-conjugated anti-CD34 antibody (Tebu bio) for 30 minutes at 4°C with PBS buffer. MNCs were also incubated with 20 µL of phycoerythrin/Cy5 (PE/Cy5)-conjugated anti-CD117 antibody (BD Biosciences, Pharmingen) for 30 minutes at 4°C with PBS buffer. After washing, the samples were centrifuged and the pellets suspended in 500 µL of PBS buffer. The percentage of CD34 and CD117-positive cells were analyzed using CellQuest software (Beckman Coulter EPICS-XL).
BM-MNC Differentiation Into Cells With Endothelial Phenotype
BM-MNC (2x106 per mL), isolated from treated or nontreated rats, were plated on 11-mm cell-culture dishes coated with gelatin (0.1%) and rat plasma vitronectin (Sigma). BM-MNCs were maintained in Endothelial basal medium for 7 days (EGM2; Bio-Whittaker) with or without antioxidant treatments (apocynin 1 mmol/L or N-acetyl-L-cysteine NAC 0.4%, Zambon France), ACE inhibitor (perindopril 10 µmol/L), or AT1R inhibitor (losartan 10 µmol/L). Nonadherent cells were then removed and adherent cells analyzed by immunochemical assay with 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine–labeled acetylated low-density lipoprotein (Dil-LDL; Tebu Bio) and FITC-labeled BS-1 lectin (Sigma). Cells were incubated in EGM2 containing Dil-LDL at 37°C for 1 hour. Cells were then fixed in 2% paraformaldehyde and incubated with FITC-labeled BS-1 lectin. Endothelial cell phenotype was revealed with double-positive staining for both Dil-LDL and BS-1 lectin and by expression of endothelial specific markers including endothelial nitric oxide (eNOS) and von Willebrand Factor (vWF). Cell numbers were counted and expressed in cells per well by using epifluorescence microscopy, as previously described.3,4 Five replicates were counted for each treated or untreated rats. Results are expressed as percentages of total cell numbers.
Progenitor Cells Proangiogenic Potential
Five hours after hindlimb ischemia, SHR received intravenous injections of 1.106 BM-MNCs isolated from treated or nontreated rats. Animals were euthanized 14 days after cell transfusion, and vascular density was determined by 3 different methods: high-definition microangiography, capillary density analysis, and laser-doppler perfusion imaging, as described above.
VEGF and eNOS Protein Expression
Gastrocnemius muscles from ischemic and nonischemic hindlimbs were thawed and homogenized in 500 µL of buffer (50 mmol/L Tris-HCl, 150 mmol/L NaCl, 1 mmol/L EDTA, 1% Triton X-100, 0.1% SDS, 1% Deoxycholate, pH 7.4) containing protease inhibitors (Boehringer-Mannheim). Proteins were separated in denaturing 9% SDS polyacrylamide gels and then blotted onto a nitrocellulose sheet (Hybond ECL, Amersham). Antibodies directed against VEGF-A (Tebu Bio), eNOS (Cell signaling), and GADPH (Sigma) were used at a dilution of 1:1000. Specific protein was detected by chemiluminescent reaction (ECL+kit, Amersham).
Reactive Oxygen Species Levels
Tissue and cellular reactive oxygen species (ROS) levels, reflecting a balance between oxidant production and removal by endogenous antioxidants, were also quantified using L-012 as described recently.21,22 BM-MNCs, isolated from WKY and SHR, were cultured in EGM2 medium with or without apocynin (1 mmol/L), NAC (0.4%), perindopril (10 µmol/L) or losartan (10 µmol/L). 7 days after cells culture, the adherent cells were lysed in 50 mmol/L Tris buffer (pH 7.5) containing protease inhibitors and centrifuged at 10 000g for 15 minutes at 4°C. Supernatants were then incubated with L-012 100 µmol/L (Wako). Luminescence was counted (Topcount NXT; Perkin Elmer) during 20 seconds after a 10-minute interval, allowing for the plates to become dark-adapted.
Statistical Analysis
Results were expressed as mean±SEM. One-way analysis of variance ANOVA was used to compare each parameter. Posthoc Bonferroni t test comparisons were then performed to identify which group differences accounted for the significant overall ANOVA. P<0.05 was considered significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Arterial Pressure
Systolic blood pressure was increased by 1.3-fold in 12-week-old SHR compared to WKY (P<0.001). As expected, administration of perindopril, losartan, and hydralazine reduced systolic blood pressure when compared to untreated SHR (P<0.001). Hindlimb ischemia did not affect systolic blood pressure when compared with groups of rats without right femoral artery ligature (see Table).
|
Postischemic Revascularization
Angiographic score, capillary density, and paw perfusion were reduced by 1.5-, 1.6-, and 1.3-fold, respectively in untreated SHR when compared to WKY (Figure 1). Interestingly, treatment with antihypertensive agents, perindopril, losartan, or hydralazine, abrogated the hypertension-induced impairment in postischemic revascularization.
|
P<0.05, We next attempted to define the molecular and cellular mechanisms associated with these changes in revascularization. We first analyzed VEGF-A protein content, a key angiogenic factor. There was not significant difference in VEGF-A expression in nonischemic groups. Under ischemic condition, VEGF-A protein levels were increased by 1.7-fold in ischemic muscle in reference to nonischemic muscle of WKY (P<0.05). VEGF-A protein content was decreased by 2.4-fold in the ischemic hindlimb of SHR compared to that of WKY (P<0.001). However, treatment with perindopril or losartan did not restore VEGF-A protein content (Figure 2).
|
VEGF-A has been shown, through Flk-1/KDR, to activate endothelial nitric oxide synthase (eNOS)-related pathways leading to NO production. We then determined eNOS expression in the different experimental groups. We showed that eNOS protein levels were not significantly different in nonischemic hindlimbs whatever the treatment. Fourteen days of hindlimb ischemia increased eNOS protein content by 1.7-fold in WKY but not in SHR (P<0.05). Interestingly, treatment with perindopril or losartan increased eNOS levels in ischemic SHR compared to untreated SHR and restored eNOS protein expression to ischemic WKY levels.
Postischemic Vasculogenesis
Proangiogenic Potential of BM-MNC
We next hypothesized that reduction in blood vessel growth may depend on the hypertension-induced BM-MNC dysfunction. Hypertension is associated with an increase in ROS levels.23 Increased oxidative stress constitutes an underlying pathogenic mechanism that affects both angiogenesis and vasculogenesis.4 We therefore evaluated the effects of hypertension-induced increased ROS levels on the ability of BM-MNCs to stimulate neovascularization.
Protein expression of NADPH oxidase subunits was detected in control BM-MNCs. Their levels were upregulated in SHR BM-MNCs versus WKY BM-MNCs (Figure 3a). ROS levels were also increased by 2.0-fold in SHR BM-MNCs compared to control BM-MNCs (P<0.001, Figure 3b). Treatment with NAC or apocynin reduced ROS levels in both control and SHR cells. Interestingly, treatments with perindopril or losartan also decreased by 1.6-fold the production of ROS levels (Figure 3b). Angiography score, capillary density, and foot perfusion were decreased by 1.4-, 1.5- (P<0.001), and 1.2-fold (P<0.05), respectively, in ischemic SHR receiving BM-MNCs isolated from untreated ischemic SHR compared to those transfused with BM-MNCs isolated from ischemic WKY. BM-MNCs from ischemic SHR treated with perindopril, losartan, or hydralazine displayed a restored proangiogenic potential when injected in untreated ischemic SHR. Interestingly, treatment with the antioxidant, NAC, also counteracted BM-MNC dysfunction (Figure 4). These results suggest that hypertension-induced oxidative stress hampers vasculogenesis, and subsequently postischemic neovascularization.
|
|
BM-MNC Differentiation Into Cells With an Endothelial Phenotype
BM-MNCs improve neovascularization of ischemic hind limbs and ischemic hearts through their capacity to integrate new blood vessels or secrete proangiogenic factors. We thus evaluated the ability of BM-MNCs to differentiate in vitro into cells with endothelial phenotype. Acquisition of endothelial cell phenotype was revealed with double-positive staining for both Dil-LDL and BS-1 lectin. The percentage of double positive cells was lower by 1.3-fold in nonischemic SHR compared to nonischemic WKY (P<0.05). Administration of perindopril or losartan did not affect the percentage of double positive cells in SHR without hindlimb ischemia. After 2 weeks of ischemia, the percentage of double positive cells was increased by 1.6-fold in ischemic WKY in reference to nonischemic WKY (P<0.001). However, the number of double positive cells was reduced in ischemic SHR compared to ischemic WKY. Similarly, the number of cells positive for both BS1-lectin/eNOS or BS-1lectin/vWF was lower by around 2-fold in SHR compared to WKY (Figure S1, available online at http://hyper.ahajournals.org). Interestingly, treatment with perindopril, losartan, and hydralazine increased the number of cells double positive for both DilLDL and BS-1 lectin by 1.7-, 1.6-, and 1.4-fold, respectively in ischemic SHR compared to untreated ischemic SHR (P<0.01; Figure 5a and 5b). Similarly, treatment with NAC or apocynin increased the number of SHR DilLDL/BS1lectin-positive cells compared to untreated SHR BM-MNCs (Figure 5c), supporting the hypothesis that the decreased differentiation of SHR BM-MNCs was mediated by enhanced ROS levels.
|
Number of Circulating Progenitor Cells
Reduction in blood vessel growth may also depend on the hypertension-induced decrease in the mobilization of progenitor cells from the bone marrow and subsequently in the number of circulating progenitor cells. We therefore analyzed the number of vascular progenitor cells in peripheral blood by FACS analysis. A population of circulating vascular progenitor cells were characterized as cells positive for both CD34 and CD117. We showed that the number of circulating CD34/CD117 double-positive cells was lower by 3.1-fold in nonischemic SHR versus nonischemic WKY (P<0.001). Interestingly, ischemia increased the number of CD34+/CD117+ cells by 1.6- and 1.7-fold, respectively in WKY and SHR compared with nonischemic groups (P<0.001). However, the number of circulating CD34+/CD117+ cells remained lower by 2.8-fold in ischemic SHR when compared to ischemic WKY (P<0.001). Treatment of SHR with perindopril or hydralazine raised the number of circulating CD34+/CD117+ in SHR with or without hindlimb ischemia (P<0.05). In contrast, treatment with losartan did not significantly affect the number of CD34+/CD117+ cells in peripheral circulation (Figure 6).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The main results of this study are that (1) hypertension impairs the number and the proangiogenic potential of progenitor cells, (2) increase of oxidative stress in the setting of hypertension participates to the altered number and efficiency of progenitor cells, and (3) antihypertensive treatments with ACE inhibitor or angiotensin type I receptor blocker restored progenitor cell–related function and subsequently postischemic revascularization.
Hypertension, a major cardiovascular risk factor, has been shown to hamper postischemic neovascularization.11 We confirm and extend these previous studies, because we demonstrated that alteration of vessel growth is related, at least in part, to a reduction in the number of circulating progenitor cells. The ability of BM-MNCs to differentiate into cells with endothelial phenotype and promote therapeutic revascularization was also strongly impaired, suggesting that hypertension hampers vasculogenesis and subsequently postischemic revascularization. Interestingly, antihypertensive agents, AT1R blocker, ACE inhibitor, and hydralazine fully abrogate hypertension-related effects. In line with these findings, treatment with the type 1 Ang II receptor antagonist olmesartan increased the number of circulating EPCs in diabetic hypertensive patients,24 and administration of ACE inhibitors was associated with high levels of these cells in patients with coronary artery disease.25 However, prolonged treatments with an ACE inhibitor, but not with AT1R antagonist, increased the number of circulating progenitor cells. Hydralazine also raised the number of circulating progenitor cells suggesting that blood pressure reduction is the principal mechanism leading to upregulation of double-positive cells in this setting. The discrepancy between perindopril and losartan administration may first depend on their blood pressure lowering effects. After 3 weeks of treatment, blood pressure tended to be lower in perindopril-treated SHR compared to losartan-treated SHR. Nevertheless, it is likely that antihypertensive drug treatment may have specific effects on proangiogenic and provasculogenic pathways. In support of this view, ACE inhibition, through activation of bradykinin signaling, upregulates VEGF and eNOS and promotes neovascularization in normotensive and hypertensive rats.26–30 VEGF and eNOS are also involved in progenitor cells mobilization from the bone marrow, BM-MNC differentiation, and progenitor cell proangiogenic function.3,31 Conversely, BM-MNCs isolated from mice lacking AT1R blockade display alterations in their proangiogenic functions.32 Therefore, non–blood pressure–dependent actions of perindopril and losartan may also be involved in their effect on the different steps of vasculogenesis.
Hypertension is associated with an increase in ROS levels.23 Increased oxidative stress constitutes an underlying pathogenic mechanism that affects both angiogenesis and vasculogenesis. In particular, we have shown that diabetes-induced increases in ROS enhanced p38MAPK phosphorylation in BM-MNCs, reduced BM-MNC differentiation into EPCs in vitro, and impaired their proangiogenic potential in vivo.4 We found that ROS levels were higher in BM-MNCs isolated from hypertensive rats, in association with the upregulation of different subunits of NADPH oxidase. We also demonstrated that hypertension-induced increases in ROS levels decreased BM-MNC differentiation into cells with endothelial phenotype in vitro and hampered their therapeutic in vivo effect. Interestingly, antihypertensive agents and the scavenging of ROS similarly restored progenitor cells proangiogenic potential. In line with these findings, ACE inhibitor and AT1R blocker have been shown to suppress ROS generation in heart of hypertensive animals with diastolic heart failure.33 In addition, both AT1R antagonist and ACE inhibitor inhibited vascular remodeling and reduced ROS in stroke-prone spontaneously hypertensive rats via not only a reduction in NAD(P)H oxidase but also an upregulation of Cu/Zn superoxide dismutase.34
Alternatively, several functions of progenitor cells might be impaired by cardiovascular risk factors. Hence, impairment in progenitor cell adhesion to endothelium might also participate to progenitor cells dysfunction in the setting of hypertension. In this view, the clonogenic and adhesion capacity of cultured EPCs was significantly lower in diabetic patients with peripheral arterial disease versus patients without.35 Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor (TNF)-
.9 Notably, thrombospondin-1 mRNA expression was significantly upregulated in diabetic EPCs, associating with the decreased EPC adhesion activity in vitro and in vivo.36 In addition, adhesion to mature endothelial cells after activation with TNF- was enhanced only in controls but not in patients with rheumatoid arthritis.37 The functional activities of isolated EPCs, such as proliferative, migratory, adhesive, and in vitro vasculogenesis capacity, were also impaired in patients with hypercholesterolemia.38 Finally, in SHR as well as in patients with essential hypertension endothelial function is impaired and may contribute to reduced vessel regeneration in this setting.15–17 In addition, AT1R blocker and ACE inhibitor have been shown to ameliorate vascular function in SHR,39,40 suggesting that restoration of endothelium function may participate at least in part to the beneficial effects of AT1R blocker and ACE inhibitor in hypertension.
In conclusion, the decrease in the number of progenitor cells and their proangiogenic function likely participates to the hypertension-induced abrogation of postischemic vessel growth. ACE inhibitor and AT1R blocker restored postnatal vasculogenesis in this setting.
Perspectives
Despite the excitement regarding the possible clinical use of EPCs, recent studies have shown that age and other risk factors for cardiovascular diseases reduce the availability of EPCs and impair their function to varying degrees. Our study suggest that hypertension may also limit the therapeutic usefulness of vascular progenitor cells. The close interaction between hypertension and blood vessel growth might also constitute a new physiopathological view of arterial hypertension and could have important consequences in the understanding of hypertension after antiangiogenic treatment. This new hypothesis is strengthened by recent studies highlighting that appearance of hypertension in patients with metastatic renal cell carcinoma receiving antiangiogenic treatment.41,42 Finally, activation of vasculogenesis after antihypertensive drugs therapy may participate to the reduction in major macrovascular and microvascular events observed in patients with stroke or type 2 diabetes.43,44
|
Acknowledgments |
|---|
Sources of Funding
J.S.S. is supported by grants from ANR "young investigator" (JC05-45445) and "ANR-05-028-01, ANR-05-022-2, Cardiovascular, Obesity and Diabetes." INSERM U689 is a partner of the European Vascular Genomics Network (EVGN), a Network of Excellence granted by the European Commission (contract No. LSHM-CT-2003-503254). This study is also supported by grants from Naturalia & Biologia (Paris, France) and Servier (Suresnes, France). Y.D. is supported by grants from Société Française d’hypertension artérielle and Merck Sharp & Dohme-chibret.
Disclosures
None.
Received December 18, 2007; first decision January 3, 2008; accepted March 28, 2008.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Aicher A, Rentsch M, Sasaki K, Ellwart JW, Fandrich F, Siebert R, Cooke JP, Dimmeler S, Heeschen C. Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ Res. 2007; 100: 581–589.
2. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004; 109: 1543–1549.
3. You D, Waeckel L, Ebrahimian TG, Blanc-Brude O, Foubert P, Barateau V, Duriez M, Lericousse-Roussanne S, Vilar J, Dejana E, Tobelem G, Levy BI, Silvestre JS. Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy. Circulation. 2006; 114: 328–338.
4. Ebrahimian TG, Heymes C, You D, Blanc-Brude O, Mees B, Waeckel L, Duriez M, Vilar J, Brandes RP, Levy BI, Shah AM, Silvestre JS. NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes. Am J Pathol. 2006; 169: 719–728.
5. Rivard A, Fabre JE, Silver M, Chen D, Murohara T, Kearney M, Magner M, Asahara T, Isner JM. Age-dependent impairment of angiogenesis. Circulation. 1999; 99: 111–120.
6. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B, Peters K, Isner JM. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol. 1999; 154: 355–363.
7. Tamarat R, Silvestre JS, Le Ricousse-Roussanne S, Barateau V, Lecomte-Raclet L, Clergue M, Duriez M, Tobelem G, Levy BI. Impairment in ischemia-induced neovascularization in diabetes: bone marrow mononuclear cell dysfunction and therapeutic potential of placenta growth factor treatment. Am J Pathol. 2004; 164: 457–466.
8. Loomans CJ, de Koning EJ, Staal FJ, Rookmaaker MB, Verseyden C, de Boer HC, Verhaar MC, Braam B, Rabelink TJ, van Zonneveld AJ. Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes. Diabetes. 2004; 53: 195–199.
9. Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC. Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation. 2002; 106: 2781–2786.
10. Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006; 48: 1012–1017.
11. Emanueli C, Salis MB, Stacca T, Gaspa L, Chao J, Chao L, Piana A, Madeddu P. Rescue of impaired angiogenesis in spontaneously hypertensive rats by intramuscular human tissue kallikrein gene transfer. Hypertension. 2001; 38: 136–141.
12. Takeshita S, Tomiyama H, Yokoyama N, Kawamura Y, Furukawa T, Ishigai Y, Shibano T, Isshiki T, Sato T. Angiotensin-converting enzyme inhibition improves defective angiogenesis in the ischemic limb of spontaneously hypertensive rats. Cardiovasc Res. 2001; 52: 314–320.
13. le Noble FA, Stassen FR, Hacking WJ, Struijker Boudier HA. Angiogenesis and hypertension. J Hypertens. 1998; 16: 1563–1572.[CrossRef][Medline] [Order article via Infotrieve]
14. Nakano N, Moriguchi A, Morishita R, Kida I, Tomita N, Matsumoto K, Nakamura T, Higaki J, Ogihara T. Role of angiotensin II in the regulation of a novel vascular modulator, hepatocyte growth factor (HGF), in experimental hypertensive rats. Hypertension. 1997; 30: 1448–1454.
15. Konishi M, Su C. Role of endothelium in dilator responses of spontaneously hypertensive rat arteries. Hypertension. 1983; 5: 881–886.
16. Luscher TF, Vanhoutte PM, Raij L. Antihypertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension. Hypertension. 1987; 9: III193–III197.[Medline] [Order article via Infotrieve]
17. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990; 323: 22–27.[Abstract]
18. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003; 348: 593–600.
19. Imanishi T, Moriwaki C, Hano T, Nishio I. Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens. 2005; 23: 1831–1837.[Medline] [Order article via Infotrieve]
20. Silvestre JS, Thery C, Hamard G, Boddaert J, Aguilar B, Delcayre A, Houbron C, Tamarat R, Blanc-Brude O, Heeneman S, Clergue M, Duriez M, Merval R, Levy B, Tedgui A, Amigorena S, Mallat Z. Lactadherin promotes VEGF-dependent neovascularization. Nat Med. 2005; 11: 499–506.[CrossRef][Medline] [Order article via Infotrieve]
21. Castier Y, Brandes RP, Leseche G, Tedgui A, Lehoux S. p47phox-dependent NADPH oxidase regulates flow-induced vascular remodeling. Circ Res. 2005; 97: 533–540.
22. Daiber A, August M, Baldus S, Wendt M, Oelze M, Sydow K, Kleschyov AL, Munzel T. Measurement of NAD(P)H oxidase-derived superoxide with the luminol analogue L-012. Free Radic Biol Med. 2004; 36: 101–111.[CrossRef][Medline] [Order article via Infotrieve]
23. Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension. 2004; 44: 248–252.
24. Bahlmann FH, de Groot K, Mueller O, Hertel B, Haller H, Fliser D. Stimulation of endothelial progenitor cells: a new putative therapeutic effect of angiotensin II receptor antagonists. Hypertension. 2005; 45: 526–529.
25. Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005; 353: 999–1007.
26. Fabre JE, Rivard A, Magner M, Silver M, Isner JM. Tissue inhibition of angiotensin-converting enzyme activity stimulates angiogenesis in vivo. Circulation. 1999; 99: 3043–3049.
27. Silvestre JS, Bergaya S, Tamarat R, Duriez M, Boulanger CM, Levy BI. Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway. Circ Res. 2001; 89: 678–683.
28. Silvestre JS, Kamsu-Kom N, Clergue M, Duriez M, Levy BI. Very-low-dose combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide induces an early and sustained increase in neovascularization in rat ischemic legs. J Pharmacol Exp Ther. 2002; 303: 1038–1043.
29. Levy BI, Duriez M, Samuel JL. Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. Am J Hypertens. 2001; 14: 7–13.[CrossRef][Medline] [Order article via Infotrieve]
30. Rakusan K, Cicutti N, Maurin A, Guez D, Schiavi P. The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats. Microvasc Res. 2000; 59: 243–254.[CrossRef][Medline] [Order article via Infotrieve]
31. Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med. 2003; 9: 1370–1376.[CrossRef][Medline] [Order article via Infotrieve]
32. Sasaki K, Murohara T, Ikeda H, Sugaya T, Shimada T, Shintani S, Imaizumi T. Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. J Clin Invest. 2002; 109: 603–611.[CrossRef][Medline] [Order article via Infotrieve]
33. Yoshida J, Yamamoto K, Mano T, Sakata Y, Nishikawa N, Nishio M, Ohtani T, Miwa T, Hori M, Masuyama T. AT1 receptor blocker added to ACE inhibitor provides benefits at advanced stage of hypertensive diastolic heart failure. Hypertension. 2004; 43: 686–691.
34. Tanaka M, Umemoto S, Kawahara S, Kubo M, Itoh S, Umeji K, Matsuzaki M. Angiotensin II type 1 receptor antagonist and angiotensin-converting enzyme inhibitor altered the activation of Cu/Zn-containing superoxide dismutase in the heart of stroke-prone spontaneously hypertensive rats. Hypertens Res. 2005; 28: 67–77.[CrossRef][Medline] [Order article via Infotrieve]
35. Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006; 26: 2140–2146.
36. Ii M, Takenaka H, Asai J, Ibusuki K, Mizukami Y, Maruyama K, Yoon YS, Wecker A, Luedemann C, Eaton E, Silver M, Thorne T, Losordo DW. Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circ Res. 2006; 98: 697–704.
37. Herbrig K, Haensel S, Oelschlaegel U, Pistrosch F, Foerster S, Passauer J. Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis. 2006; 65: 157–163.
38. Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH, Zhu JH. Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond). 2004; 107: 273–280.[Medline] [Order article via Infotrieve]
39. Riveiro A, Mosquera A, Alonso M, Calvo C. Angiotensin II type 1 receptor blocker irbesartan ameliorates vascular function in spontaneously hypertensive rats regardless of oestrogen status. J Hypertens. 2002; 20: 1365–1372.[CrossRef][Medline] [Order article via Infotrieve]
40. Potenza MA, Marasciulo FL, Tarquinio M, Quon MJ, Montagnani M. Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. Diabetes. 2006; 55: 3594–3603.
41. Mourad JJ, des Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol. 2007.
42. Azizi M, Chedid A, Oudard S. Home blood-pressure monitoring in patients receiving sunitinib. N Engl J Med. 2008; 358: 95–97.
43. Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003; 362: 1527–1535.[CrossRef][Medline] [Order article via Infotrieve]
44. Patel A, MacMahon S, Chalmers J, Neal B, Woodward M, Billot L, Harrap S, Poulter N, Marre M, Cooper M, Glasziou P, Grobbee DE, Hamet P, Heller S, Liu LS, Mancia G, Mogensen CE, Pan CY, Rodgers A, Williams B. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007; 370: 829–840.[CrossRef][Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  J. S. Silvestre and B. I. Levy Circulating progenitor cells and cardiovascular outcomes: latest evidence on angiotensin-converting enzyme inhibitors Eur. Heart J. Suppl., August 1, 2009; 11(suppl_E): E17 - E21. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||