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Updated: May 28, 2026

A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model
Published on: November 18, 2022
Up-Regulation of the TRPM8 Channel Attenuates TRPC1-Mediated Store-Operated Calcium Entry in Abdominal Aortic
Yi-Qian Wang1,2, Min Pan1,2, Yi-Chen Lin2,3,4
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China.
Abstract:
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by vascular smooth muscle cell (VSMC) dysfunction and disrupted calcium homeostasis. While transient receptor potential canonical 6 (TRPC6) and transient receptor potential canonical 1 (TRPC1) are known to mediate receptor-operated calcium entry (ROCE) and store-operated calcium entry (SOCE), respectively, the specific contributions of SOCE and ROCE to AAA pathogenesis, and the regulatory interaction between transient receptor potential melastatin 8 (TRPM8) and TRPC1 remain unexplored. In this study, we analyzed human AAA tissues, a papain-induced mouse model, and angiotensin II (Ang II)-treated human aortic smooth muscle cells using histology, wire myography, calcium imaging, and patch-clamp electrophysiology. We observed significant upregulation of TRPM8, TRPC1, and TRPC6 in both human and experimental AAA, with TRPC1 identified as a key mediator of SOCE under pathological conditions. Pharmacological activation of TRPM8 by menthol attenuated TRPC1-mediated SOCE and associated vasoconstriction, effects that were partially reversed by the TRPM8 antagonist A-2. In Ang II-treated cells, TRPM8 activation reduced SOCE and store-operated calcium currents (ISOCC), effects that were largely abolished by TRPC1 knockdown. These findings suggest that TRPM8 may limit excessive calcium ion (Ca2+) influx and vascular remodeling in AAA, pointing to a potential endogenous mechanism to counteract maladaptive calcium signaling in AAA progression.
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