Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat

Massimiliano Mancini, Enrico Petretto, Christina Kleinert, Angela Scavone, Tisham De, Stuart Cook, Jan Silhavy, Vaclav Zidek, Michal Pravenec, Giulia D'Amati, Paolo G. Camici

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms underlying coronary microvascular remodeling and dysfunction, which are critical determinants of abnormal myocardial blood flow regulation in human hypertension, are poorly understood. The spontaneously hypertensive rat (SHR) exhibits many features of human hypertensive cardiomyopathy. We demonstrate that remodeling of intramural coronary arterioles is apparent in the SHR already at 4 weeks of age, i.e. before the onset of systemic hypertension. To uncover possible genetic determinants of coronary microvascular remodeling, we carried out detailed histological and histomorphometric analysis of the heart and coronary vasculature in 30 weeks old SHR, age-matched Brown Norway (BN-Lx) parentals and BXH/HXB recombinant inbred (RI) strains. Using previously mapped expression quantitative trait loci (eQTLs), we carried out a genome-wide association analysis between genetic determinants of cardiac gene expression and histomorphometric traits. This identified 36 robustly mapped eQTLs in the heart which were associated with medial area of intramural coronary arterioles [false discovery rate (FDR) ~5 %]. Transcripts, which were both under cis-acting genetic regulation and significantly correlated with medial area (FDR

Original languageEnglish
Article number316
JournalBasic Research in Cardiology
Volume108
Issue number1
DOIs
Publication statusPublished - 2013

Keywords

  • Arterial hypertension
  • Candidate genes
  • Coronary circulation
  • Myocardial ischemia
  • Recombinant inbred strains
  • Spontaneously hypertensive rat

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Fingerprint Dive into the research topics of 'Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat'. Together they form a unique fingerprint.

Cite this