RhoA accelerates atherosclerosis progression by interacting with Hspa5.

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Biology

Background:

• Atherosclerosis (AS) is a complex cardiovascular disease.
• The precise regulatory mechanisms of RhoA in AS remain unclear.

Purpose of the Study:

• To investigate the role and underlying mechanisms of RhoA in AS progression.
• To explore the interaction between RhoA and Hspa5 in the context of AS.

Main Methods:

• Established a high-fat diet-induced AS mouse model.
• Utilized adeno-associated viruses for RhoA manipulation in vivo.
• Analyzed oxidized low-density lipoprotein (ox-LDL) treated mouse aortic vascular smooth muscle cells (MOVAS) using various assays (cell counting kit-8, Transwell migration, electron microscopy, western blotting).
• Investigated RhoA-Hspa5 interaction via bioinformatic analysis, co-immunoprecipitation, and immunofluorescence.

Main Results:

• RhoA was significantly upregulated in AS mice and localized in the aortic smooth muscle layer.
• RhoA inhibition suppressed MOVAS cell viability, migration, invasion, and mitophagy in vitro, and reduced AS plaque formation and inflammation in vivo.
• Hspa5 was identified to interact with RhoA, with its expression positively correlated to RhoA levels.
• Hspa5 overexpression reversed the inhibitory effects of RhoA silencing on cellular behaviors and AS progression.

Conclusions:

• RhoA promotes AS by enhancing vascular smooth muscle cell migration, invasion, and mitophagy through interaction with Hspa5.
• RhoA plays a critical role in exacerbating AS progression.
• RhoA represents a potential therapeutic target for managing atherosclerosis.