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 language | English |
|---|---|
| Article number | 316 |
| Journal | Basic Research in Cardiology |
| Volume | 108 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 |
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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 journal › Article
}
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 -