miR-26a inhibits atherosclerosis progression by targeting TRPC3

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Vascular Biology

Background:

• Atherosclerosis is a chronic vascular disease contributing to cardiovascular disorders.
• MicroRNA-26a (miR-26a) has been implicated in atherosclerosis, but its precise mechanism requires further elucidation.

Purpose of the Study:

• To investigate the role and mechanism of miR-26a in the development of atherosclerosis.
• To determine if miR-26a targets transient receptor potential canonical 3 (TRPC3) and its downstream effects.

Main Methods:

• Established high-fat diet (HFD)-fed apolipoprotein E knockout (apoE-/-) mice and oxidized low-density lipoprotein (ox-LDL)-stimulated human aortic endothelial cells (HAECs) as atherosclerosis models.
• Utilized RT-qPCR, western blot, dual luciferase reporter assay, and various biochemical and histological analyses to assess miR-26a, TRPC3, lipid accumulation, atherosclerotic lesions, and inflammatory markers.

Main Results:

• miR-26a expression was reduced in atherosclerosis models.
• Overexpression of miR-26a attenuated hyperlipidemia, atherosclerotic lesions, and inflammation in mice.
• In HAECs, miR-26a suppressed inflammation, promoted cell viability, and inhibited apoptosis by targeting TRPC3 and the NF-κB pathway.
• TRPC3 was confirmed as a direct target of miR-26a, and its enforced expression reversed miR-26a's protective effects.

Conclusions:

• miR-26a plays a protective role in atherosclerosis by downregulating TRPC3.
• miR-26a represents a promising therapeutic target for managing atherosclerosis.