[Vascular smooth muscle cell response to cyclic mechanical stretch and aortic dissection]

Area of Science:

• Cardiovascular Biology
• Vascular Cell Biology
• Mechanobiology

Background:

• Acute aortic dissection is a critical vascular condition with high mortality.
• Pulsatile blood flow causes cyclic mechanical stretch (CMS) on vascular smooth muscle cells (VSMCs), leading to cell death and dissection.
• Understanding VSMC responses to CMS is crucial for preventing aortic dissection.

Purpose of the Study:

• To investigate the mechanisms of VSMC death induced by CMS.
• To evaluate the protective effects of azelnidipine, olmesartan, and chemokine signaling against CMS-induced VSMC death.
• To explore the role of JNK, p38, and STAT1 activation in VSMC stress responses.

Main Methods:

• Cultured rat aortic smooth muscle cells (RASMCs) subjected to CMS.
• Treatment with calcium channel blockers (azelnidipine), angiotensin II receptor antagonists (olmesartan), and specific inhibitors.
• Analysis of JNK and p38 phosphorylation, cell death, and chemokine (Cxcl1, Cx3cl1) expression.
• In vivo study using mouse models of hypertension.

Main Results:

• CMS induced JNK- and p38-dependent cell death in RASMCs.
• Azelnidipine and olmesartan reduced JNK/p38 phosphorylation and CMS-induced cell death.
• CMS induced Cxcl1 and Cx3cl1 expression in a JNK-dependent manner, and these chemokines protected cells from death.
• STAT1 activation was observed in RASMCs under CMS.

Conclusions:

• CMS activates inflammatory gene expression and JNK/p38 MAP kinases in VSMCs, contributing to cell death.
• Pharmacological agents like azelnidipine and olmesartan, along with chemokines CXCL1 and CX3CL1, show potential in mitigating CMS-induced VSMC damage.
• These findings highlight key pathways involved in the VSMC stress response to hypertension and aortic dissection.