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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1810.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Monocyte Chemoattractant Proteins Mediate Myocardial Microvascular Dysfunction in Swine Renovascular Hypertension

Jing Lin; Xiangyang Zhu; Alejandro R. Chade; Kyra L. Jordan; Ronit Lavi; Elena Daghini; Matthew E. Gibson; Angelo Guglielmotti; Amir Lerman; Lilach O. Lerman

From the Division of Nephrology and Hypertension (J.L., X.Z., A.R.C., K.L.J., R.L., E.D., M.E.G., L.O.L.) and Cardiovascular Diseases (A.L., L.O.L.), Mayo Clinic, Rochester, Minn; and the Angelini Research Center (A.G.), ACRAF, S. Palomba-Pomezia, Rome, Italy. Current affiliation for A.R.C.: the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson. Current affiliation for R.L.: the Department of Anesthesia and Perioperative Medicine, London Health Care Science Center, University of Western Ontario, Canada.

Correspondence to Lilach O. Lerman, MD, PhD, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail lerman.lilach{at}mayo.edu

Background— Monocyte chemoattractant proteins (MCPs) play an important role in mediating inflammatory processes. Hypertension (HTN) is associated with inflammation as well as impaired cardiac microcirculatory function and structure, but the contribution of MCPs to these alterations remained unclear. This study tested the hypothesis that MCPs regulate cardiac microvascular function and structure in experimental HTN.

Methods and Results— Pigs (n=6 per group) were studied after 10 weeks of normal, renovascular HTN, or renovascular HTN+ bindarit (MCPs inhibitor, 50 mg/kg/d PO). Left ventricular (LV) function, myocardial microvascular permeability, and fractional vascular volume were assessed by fast computed tomography before and after adenosine infusion (400 µg/kg/min). Myocardial fibrosis, inflammation, and microvascular remodeling were determined ex vivo. Hypertension was not altered by bindarit, but LV hypertrophy and diastolic function were improved. In response to adenosine, myocardial microvascular permeability increased in HTN (from 0.0083±0.0009 to 0.0103±0.0011 AU, P=0.038 versus baseline) and fractional vascular volume decreased, whereas both remained unchanged in normal and HTN+bindarit pigs. HTN upregulated endothelin-1 expression, myocardial inflammation, and microvascular wall thickening, which were inhibited by bindarit.

Conclusions— MCPs partly mediate myocardial inflammation, fibrosis, vascular remodeling, and impaired vascular integrity induced by hypertension. Inhibition of MCPs could potentially be a therapeutic target in hypertensive cardiomyopathy.

This study tested the hypothesis that monocyte chemoattractant proteins (MCPs) regulate cardiac microvascular function and structure in experimental hypertension. Pigs with renovascular hypertension were studied after treatment with bindarit (MCPs inhibitor). It was found that MCPs partly mediate myocardial fibrosis, vascular remodeling, and impaired vascular integrity induced by hypertension.

Key Words: MCPs • inflammation • hypertension • microvascular permeability • remodeling