My laboratory is interested in bi-directional crosstalk between vascular endothelium and cardiomyocytes that regulates cardiac size and function. As an alternative to myocyte-driven hypertrophy in response to hemodynamic stress we recently reported a cross-talk loop induction of myocardial hypertrophy by expanding vascular endothelium in the absence of traditional hypertrophy stimuli. This reveals a new and unexplored role played by the endothelium in regulation of adult organ growth and size that would be of great interest in formulating new therapeutic angiogenic approaches to the treatment of heart disease.
Our hypothesis is that an increase in vascular endothelium in the adult heart results in increased nitric oxide (NO) production that in turn drives the growth of cardiomyocytes by sustained ubiquitination of the negative regulator of G protein signaling subtype 4 (RGS4) and derepression of the hypertrophic program via heterotrimeric G protein signaling. To investigate this crosstalk we use cell culture and conditional mouse models.