Serum exosomes derived from spontaneously hypertensive rats induce cardiac hypertrophy in vitro and in vivo by increasing autocrine release of angiotensin II in cardiomyocytes

Abstract

Identifying the key factors mediating the progression from hypertension to cardiac hypertrophy is critically important for developing a strategy to protect against heart failure. Serum exosomes have been revealed to be involved in the development of cardiovascular disease. In the current study, we found that either serum or serum exosomes derived from SHR induced hypertrophy in H9c2 cardiomyocytes. SHR Exo injection through the tail vein for 8 weeks induced left ventricular wall thickening and decreased cardiac function in C57BL/6 mice. SHR Exo carried the renin-angiotensin system (RAS) proteins AGT, renin, and ACE into cardiomyocytes, which increased the autocrine secretion of Ang II. Moreover, the AT1-type receptor antagonist telmisartan prevented hypertrophy of H9c2 cells induced by SHR Exo.These results identified a novel role of exosomes derived from SHR serum in cardiac hypertrophy and revealed that SHR Exo induced cardiac hypertrophy by carrying AGT, renin, and ACE proteins into cardiomyocytes to increase their autocrine secretion of Ang II. The emergence of this new mechanism will help us better understand how hypertension progresses to cardiac hypertrophy.

Keywords: Angiotensin II; Cardiac hypertrophy; Exosome; Hypertension.