Heart failure is characterized by a relentless progression of signs and symptoms. A relatively long interval (several
years) exists between the precipitating events that induce myocardial damage followed by a functional compensated
period and the final state termed dilated cardiomyopathy. Dilated cardiomyopathy is characterized by markedly enlarged
heart chambers and impaired contractile function. Delineating the molecular and cellular mechanisms that initiate and
mediate the pathogenesis of heart failure during this long interval still remains an enormous challenge, and is the long-
term goal of the project.
A commonly accepted paradigm for the development of heart failure divides the pathological process into two distinct
stages: initial compensatory hypertrophy to keep up with the body demand for blood supply, followed by a critical
transition to decompensated failure under persistent stress.
Epigenomic regulation is emerging as a new mechanism contributing to the initiation, development and prognosis of
heart failure, and next-generation sequencing technologies have made it possible to dissect this complicated regulatory
In this study, the investigators started with a set of unbiased genome-scale high-throughput screenings in both human
and animal failing hearts, and uncovered several potential epigenetic regulators that might be critical for the progression
of heart failure including initial stage of cardiac hypertrophy and the later failing stage. A set of comprehensive
bioinformatics analyses, molecular biology experiments and genetic animal models are applied to investigate this new
mechanism. The eventual results will allow a look from a different angle to understand the progression of HF. The
manipulation of the uncovered mechanism could be a novel therapeutic strategy for the heart failure treatment in patients.