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 journalArticle

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

Fingerprint

Inbred SHR Rats
Quantitative Trait Loci
Arterioles
Hypertension
Genome-Wide Association Study
Norway
Cardiomyopathies
Gene Expression

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

Cite this

Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat. / Mancini, Massimiliano; Petretto, Enrico; Kleinert, Christina; Scavone, Angela; De, Tisham; Cook, Stuart; Silhavy, Jan; Zidek, Vaclav; Pravenec, Michal; D'Amati, Giulia; Camici, Paolo G.

In: Basic Research in Cardiology, Vol. 108, No. 1, 316, 2013.

Research output: Contribution to journalArticle

Mancini, M, Petretto, E, Kleinert, C, Scavone, A, De, T, Cook, S, Silhavy, J, Zidek, V, Pravenec, M, D'Amati, G & Camici, PG 2013, 'Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat', Basic Research in Cardiology, vol. 108, no. 1, 316. https://doi.org/10.1007/s00395-012-0316-y
Mancini, Massimiliano ; Petretto, Enrico ; Kleinert, Christina ; Scavone, Angela ; De, Tisham ; Cook, Stuart ; Silhavy, Jan ; Zidek, Vaclav ; Pravenec, Michal ; D'Amati, Giulia ; Camici, Paolo G. / Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat. In: Basic Research in Cardiology. 2013 ; Vol. 108, No. 1.
@article{2319904869d34b9594bb5c0734f3a760,
title = "Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat",
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",
keywords = "Arterial hypertension, Candidate genes, Coronary circulation, Myocardial ischemia, Recombinant inbred strains, Spontaneously hypertensive rat",
author = "Massimiliano Mancini and Enrico Petretto and Christina Kleinert and Angela Scavone and Tisham De and Stuart Cook and Jan Silhavy and Vaclav Zidek and Michal Pravenec and Giulia D'Amati and Camici, {Paolo G.}",
year = "2013",
doi = "10.1007/s00395-012-0316-y",
language = "English",
volume = "108",
journal = "Basic Research in Cardiology",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "1",

}

TY - JOUR

T1 - Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat

AU - Mancini, Massimiliano

AU - Petretto, Enrico

AU - Kleinert, Christina

AU - Scavone, Angela

AU - De, Tisham

AU - Cook, Stuart

AU - Silhavy, Jan

AU - Zidek, Vaclav

AU - Pravenec, Michal

AU - D'Amati, Giulia

AU - Camici, Paolo G.

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

KW - Arterial hypertension

KW - Candidate genes

KW - Coronary circulation

KW - Myocardial ischemia

KW - Recombinant inbred strains

KW - Spontaneously hypertensive rat

UR - http://www.scopus.com/inward/record.url?scp=84870054198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870054198&partnerID=8YFLogxK

U2 - 10.1007/s00395-012-0316-y

DO - 10.1007/s00395-012-0316-y

M3 - Article

C2 - 23197152

AN - SCOPUS:84870054198

VL - 108

JO - Basic Research in Cardiology

JF - Basic Research in Cardiology

SN - 0300-8428

IS - 1

M1 - 316

ER -