UC San Diego

The cardiovascular system modifies its function and structure in response to various stimuli, affecting hemodynamic variables such as arterial blood pressure and blood flow rate. Mechanical stimuli are one such factor, in many cases eliciting a cellular response. The responses are mediated by mechanotransduction, the mechanism by which cells convert mechanical stimuli into chemical activity. There have been extensive studies on the effects of mechanical forces and subsequent mechanotransduction in various cell types. For example, in neonatal rat ventricular myocytes, fluid shear has been shown to affect their intrinsic beating rate. Also, in cardiac myocytes, stretching has been implicated in cellular hypertrophy. However, whether fluid shear stress imposed on the outer membrane of myocytes elicits a hypertrophic response remains unknown. In vivo, cardiac myocytes experience fluid shear stress from the interstitial fluid between sliding layers of myocytes, and possibly due to blood flow in the heart chambers. Using a parallel plate flow chamber, fluid shear of similar magnitude experienced by myocytes in vivo can be applied. To examine the possible role of fluid shear on cardiac hypertrophy, a fluid flow chamber was used to apply shear stress on myocytes. Next, genes commonly upregulated in a hypertrophic response, such as that of atrial natriuretic factor (ANP) and brain natriuretic factor (BNP), was measured and compared to a baseline control. It was found that neonatal rat ventricular myocytes do respond to fluid shear by increasing BNP expression, indicating a novel mechanotransduction mechanism in load induced hypertrophy.