(Hypertension. 2000;36:360.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II–Induced Hypertension
From the Department of Medicine (W.R.T.), Cardiology Division, Atlanta VA Medical Center, and Emory University School of Medicine (E.B., J.N.W., H.D., M.H., W.R.T.), Atlanta, Ga; and Department of Pathology (N.M., W.A.K., T.C.D.), University of North Carolina, Chapel Hill, NC.
Correspondence to W. Robert Taylor, MD, PhD, Cardiology Division, Emory University School of Medicine, 1639 Pierce Dr, Suite WMB 319, Atlanta, GA 30322. E-mail wtaylor{at}emory.edu
Abstract—Recent studies have
identified the presence of macrophages in the
arterial wall of hypertensive animals and suggested that as
is the case in atherosclerosis, macrophage
products may be important mediators of the adaptive response of the
arterial wall. In support of this, we have previously shown
that the expression of monocyte chemoattractant protein-1 is
upregulated in the arteries of hypertensive animals. We hypothesized
that macrophage recruitment is a critical step in the
pathogenesis of hypertension. To obtain insights into this potential
mechanism, we made use of mice deficient in the CC chemokine receptor 2
(CCR2), the receptor for monocyte chemoattractant protein-1.
Hypertension was induced with the subcutaneous administration of
angiotensin II (0.75 mg · kg-1 ·
d-1) for 7 days. Using in situ hybridization with a probe
for c-fms to identify macrophages, we found that
hypertension-induced macrophage infiltration of the
arterial wall was virtually eliminated in CCR2-deficient
mice. In addition, vascular hypertrophy was reduced by
65% compared with wild-type animals. These data demonstrate that
CCR2 is essential for the recruitment of macrophages into the
arterial wall in the setting of hypertension. Furthermore,
the decreased hypertrophic response suggests that vascular
hypertrophy occurs in part as a consequence of
macrophage infiltration. In angiotensin II–induced
hypertension, CCR2-mediated responses are critical to the process of
macrophage recruitment and vascular hypertrophy and
may represent one mechanism by which at least some forms of
hypertension may lead to the development of atherosclerosis.
Key Words: proteins • angiotensin II • hypertrophy • macrophages
This article has been cited by other articles:
 |
|
 |
|
  A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-D. Liao, X.-P. Yang, Y.-H. Liu, E. G. Shesely, M. A. Cavasin, W. A. Kuziel, P. J. Pagano, and O. A. Carretero Role of Inflammation in the Development of Renal Damage and Dysfunction in Angiotensin II-Induced Hypertension Hypertension, August 1, 2008; 52(2): 256 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Weiss and W. R. Taylor Deoxycorticosterone Acetate Salt Hypertension in Apolipoprotein E-/- Mice Results in Accelerated Atherosclerosis: The Role of Angiotensin II Hypertension, February 1, 2008; 51(2): 218 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Pagano and D. D. Gutterman The adventitia: The outs and ins of vascular disease Cardiovasc Res, September 1, 2007; 75(4): 636 - 639. [Full Text] [PDF]
|
|
|
|
|
|
K. Maiellaro and W. R. Taylor The role of the adventitia in vascular inflammation Cardiovasc Res, September 1, 2007; 75(4): 640 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Haurani and P. J. Pagano Adventitial fibroblast reactive oxygen species as autacrine and paracrine mediators of remodeling: Bellwether for vascular disease? Cardiovasc Res, September 1, 2007; 75(4): 679 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Ko, F. Amiri, N. R. Pandey, D. Javeshghani, E. Leibovitz, R. M. Touyz, and E. L. Schiffrin Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1789 - H1795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Buga, J. S. Frank, G. A. Mottino, M. Hendizadeh, A. Hakhamian, J. H. Tillisch, S. T. Reddy, M. Navab, G. M. Anantharamaiah, L. J. Ignarro, et al. D-4F decreases brain arteriole inflammation and improves cognitive performance in LDL receptor-null mice on a Western diet J. Lipid Res., October 1, 2006; 47(10): 2148 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ardanaz and P. J. Pagano Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Experimental Biology and Medicine, March 1, 2006; 231(3): 237 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, K. K. Griendling, A. Dikalova, G. K. Owens, and W. R. Taylor Vascular Hypertrophy in Angiotensin II-Induced Hypertension Is Mediated by Vascular Smooth Muscle Cell-Derived H2O2 Hypertension, October 1, 2005; 46(4): 732 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Shah Role of the renin-angiotensin system in the pathogenesis of preeclampsia Am J Physiol Renal Physiol, April 1, 2005; 288(4): F614 - F625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kanda, K. Hayashi, S. Wakino, K. Homma, K. Yoshioka, K. Hasegawa, N. Sugano, S. Tatematsu, I. Takamatsu, T. Mitsuhashi, et al. Role of Rho-Kinase and p27 in Angiotensin II-Induced Vascular Injury Hypertension, April 1, 2005; 45(4): 724 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Weber, P. Rocic, A. M. Mellis, K. Laude, A. N. Lyle, D. G. Harrison, and K. K. Griendling Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22phox in vascular smooth muscle Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H37 - H42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Seo, T. Wang, H. Dressman, E. E. Herderick, E. S. Iversen, C. Dong, K. Vata, C. A. Milano, F. Rigat, J. Pittman, et al. Gene Expression Phenotypes of Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1922 - 1927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, A. Ormsby, N. Oja-Tebbe, and P. J. Pagano Gene Transfer of NAD(P)H Oxidase Inhibitor to the Vascular Adventitia Attenuates Medial Smooth Muscle Hypertrophy Circ. Res., September 17, 2004; 95(6): 587 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhao, M. Ishibashi, K.-i. Hiasa, C. Tan, A. Takeshita, and K. Egashira Essential Role of Vascular Endothelial Growth Factor in Angiotensin II-Induced Vascular Inflammation and Remodeling Hypertension, September 1, 2004; 44(3): 264 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishibashi, K.-i. Hiasa, Q. Zhao, S. Inoue, K. Ohtani, S. Kitamoto, M. Tsuchihashi, T. Sugaya, I. F. Charo, S. Kura, et al. Critical Role of Monocyte Chemoattractant Protein-1 Receptor CCR2 on Monocytes in Hypertension-Induced Vascular Inflammation and Remodeling Circ. Res., May 14, 2004; 94(9): 1203 - 1210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ni, S. Kitamoto, M. Ishibashi, M. Usui, S. Inoue, K.-i. Hiasa, Q. Zhao, K.-i. Nishida, A. Takeshita, and K. Egashira Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 534 - 539. [Abstract] [Full Text]
|
|
|
|
|
|
K. Saraff, F. Babamusta, L. A. Cassis, and A. Daugherty Aortic Dissection Precedes Formation of Aneurysms and Atherosclerosis in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1621 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Izawa, Y. Yamada, T. Okada, M. Tanaka, H. Hirayama, and M. Yokota Prediction of Genetic Risk for Hypertension Hypertension, May 1, 2003; 41(5): 1035 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, V. Esteban, Y. Suzuki, S. Mezzano, J.J. Plaza, and J. Egido Role of the Renin-Angiotensin System in Vascular Diseases: Expanding the Field Hypertension, December 1, 2001; 38(6): 1382 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Hilgers, A. Hartner, M. Porst, R. Veelken, and J. F.E. Mann Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension: Relation to Kidney Inflammation Circulation, September 18, 2001; 104(12): 1436 - 1440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Luft Workshop: Mechanisms and Cardiovascular Damage in Hypertension Hypertension, February 1, 2001; 37(2): 594 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Wang, S. Xu, D. G. Johns, Y. Du, M. T. Quinn, A. J. Cayatte, and R. A. Cohen Role of NADPH Oxidase in the Vascular Hypertrophic and Oxidative Stress Response to Angiotensin II in Mice Circ. Res., May 9, 2001; 88(9): 947 - 953. [Abstract] [Full Text] [PDF]
|
|