Transcriptional network analysis for the regulation of left ventricular hypertrophy and microvascular remodeling.
Hypertension and cardiomyopathies share maladaptive changes of cardiac morphology, eventually leading to heart failure. These include left ventricular hypertrophy (LVH), myocardial fibrosis, and structural remodeling of coronary microcirculation, which is the morphologic hallmark of coronary microvascular dysfunction. To pinpoint the complex molecular mechanisms and pathways underlying LVH-associated cardiac remodeling independent of blood pressure effects, we employed gene network approaches to the rat heart. We used the Spontaneously Hypertensive Rat model showing many features of human hypertensive cardiomyopathy, for which we collected histological and histomorphometric data of the heart and coronary vasculature, and genome-wide cardiac gene expression. Here, we provide a large catalogue of gene co-expression networks in the heart that are significantly associated with quantitative variation in LVH, microvascular remodeling, and fibrosis-related traits. Many of these networks were significantly conserved to human idiopathic and/or ischemic cardiomyopathy patients, suggesting a potential role for these co-expressed genes in human heart disease.
Medical Research Council (MRC) Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Imperial Centre for Translational and Experimental Medicine (ICTEM) Building, Du Cane Road, London, W12 0NN, UK.
Aida
A
Moreno-Moral
Massimiliano
M
Mancini
Giulia
G
D'Amati
Paolo
P
Camici
Enrico
E
Petretto
D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D006973:Hypertension / Q000150:complications; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology; D040641:Quantitative Trait Loci; D051381:Rats; D011918:Rats, Inbred SHR; D013045:Species Specificity; D016277:Ventricular Function, Left / Q000235:genetics*; D020257:Ventricular Remodeling / Q000235:genetics*