Expression of renin-angiotensin system and extracellular matrix genes in cardiovascular cells and its regulation through AT1 receptor

Angiotensinogen (AGT) is a unique substrate of the renin-angiotensin system and fibronectin (FN) is an important component of the extracellular matrix . These play critical roles in the pathophysiological changes including car diovascular remodeling and hypertrophy in response to hypertension. This st udy was performed to examine the regulation of AGT and FN gene in cardiac m yocytes (CMs) and vascular smooth muscle cells (VSMCs) in response to mecha nical stretch. Mechanical stretch significantly increased the AGT mRNA expr ession in CMs, while these stimuli did not affect FN mRNA levels. On the ot her hand, Mechanical stretch upregulated FN mRNA levels in VSMCs, whereas n o increase in AGT mRNA levels was observed in response to stretch stimuli. An angiotensin II type 1 (AT1) receptor antagonist (CV11974) significantly decreased these stretch-mediated increases in mRNA level and promoter activ ity of the AGT and FN gene, whereas angiotensin II type 2 (AT2) receptor an tagonist (PD123319) did not affect the induction. These results indicate th at mechanical stretch activates transcription of the AGT and FN gene mainly via AT1 receptor-pathway in CMs and VSMCs. Furthermore, mechanisms regulat ing AGT and FN gene seem to be different between CMs and VSMCs.