This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Sarwar, R. Articles by Cook, S. A. PubMed PubMed Citation Articles by Sarwar, R. Articles by Cook, S. A. Related Collections Congestive Animal models of human disease Genomics Hypertrophy Physiological and pathological control of gene expression Genetics of cardiovascular disease

(Circulation. 2009;120:437-444.)
© 2009 American Heart Association, Inc.

Basic Science for Clinicians

Genomic Analysis of Left Ventricular Remodeling

Rizwan Sarwar, MRCP; Stuart A. Cook, PhD, MRCP

From the Medical Research Council Clinical Sciences Centre (R.S., S.A.C.) and National Heart and Lung Institute (S.A.C.), Imperial College, London, United Kingdom.

Correspondence to Dr Stuart Cook, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Rd, London, W12 0NN, UK. E-mail stuart.cook@csc.mrc.ac.uk

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The left ventricle (LV) of the heart remodels in response to hemodynamic load through the processes of physiological or pathophysiological hypertrophy.^1–3 Despite extensive study of the molecular basis of cardiac hypertrophy and LV remodeling,^1,4 the mainstay of medical treatment of maladaptive remodeling remains based on therapies initially devised for treating hypertension. The limited progress in the development of specific therapies for LV remodeling has led some to refer to "the impossible task of developing a new treatment for heart failure" and is the reason why, in part, device therapies have received such recent attention.^5–8 To gain a better understanding of the biology of maladaptive LV remodeling, with a view to identifying therapeutic targets, new paradigms and experimental approaches are needed, and genomics provides one such methodology.

Genomics is the study of genome-scale data sets, at the DNA or RNA level, and when combined with studies of physiological traits or disease phenotypes, genomics can be used to infer molecular insights. Unlike single-gene studies, which are the favored hypothesis-driven design,⁴ genomic approaches examine variation in up to gigabases of sequences to find statistical associations between transcripts and traits in a hypothesis-free system. These hypothesis-free studies have often been criticized as unfocused, but following the successes of genome-wide association studies (GWAS) and the recent achievements of integrated genetic and genomic analyses, a new era of genomic experimentation presents itself.^9–14 It is notable that GWAS and integrated genomic studies in humans often identify regions associated with disease rather than specific genes and that effect . . . [Full Text of this Article]