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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1810-1816
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number11
DOIs
StatePublished - Nov 2009

Keywords

  • Hypertension
  • Inflammation
  • MCPs
  • Microvascular permeability
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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