Background:TRPC6 channel proteins are widely distributed in the cardiovascular system, and alterations in channel function or expression are associated with a variety of vascular diseases, including atherosclerosis. Previous studies have shown that mild repetitive traumatic brain injury impairs vascular endothelial function, and this process is associated with the activation of TRPC6. The occurrence of AS is closely related to vascular endothelial function injury, so mTBI acceleration of AS may be related to endothelial TRPC6 channels.
Objective: To investigate the effects of repetitive mild TBI mediated changes in TRPC6 channel expression and function on atherosclerotic lesions in mice.
Methods: Male ApoE-/- mice of about 15 weeks were divided into mTBI and sham groups, with 12 mice in each group. TRPC6-KO mice under the ApoE-/- background were also divided into mTBI and sham groups, with 12 mice in each group. The mice in the TBI group were subjected to craniocerebral shock every 72 hours to induce mild TBI, a total of three times. After 10 weeks, the blood vessels of heart and aorta of model mice were collected and stained by Red Oil O, Masson's Trichrome, Evans Blue, and immunohistochemistry (specific a-actin, VCAM-1, MAC-3, and TRPC6 staining). The area and cell composition of atherosclerotic plaques in the RMTBI group and the Sham group were analyzed. Aortic vascular tension and endothelial diastolic function were measured using an isotonic tension test system.
Results: The area of atherosclous plaque in ApoE-/- mice mTBI group was significantly larger than that in Sham group, indicating that the endothelial function of TRPC6 knockout mice under repeated mild ApoE-/- background was improved compared with that of ApoE-/- mice, confirming that rmTBI promotion of AS is related to the expression or function of TRPC6 channel. This channel may be a new target for the treatment and prevention of late atherosclerosis in patients with mTBI.