Background:
Transient receptor potential (TRP) channels, especially canonical TRP channel subfamily
members 3 (TRPC3) and 6 (TRPC6), have attracted attention as a putative therapeutic target of heart
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failure. Moreover, TRPC3 and TRPC6 channels are physiologically important for maintaining cellular
homeostasis. How TRPC3/C6 channels alter intracellular signaling from adaptation to maladaptation has
been discussed for many years. We recently showed that formation of a protein signal complex between
TRPC3 and NADPH oxidase (Nox) 2 caused by environmental stresses (e.g., hypoxia, nutritional
deficiency, and anticancer drug treatment) promotes Nox2-dependent reactive oxygen species production
and cardiac stiffness, including myocardial atrophy and interstitial fibrosis, in rodents. In fact,
pharmacological prevention of the TRPC3-Nox2 protein complex can maintain cardiac flexibility in mice
after anti-cancer drug treatment.
Conclusion:
In this mini-review, we discuss the relationship between TRPC3/C6 channels and
cardiovascular disease, and propose a new therapeutic strategy by focusing on pathology-specific protein–
protein interactions.