Abstract
Transient receptor potential (TRP) channels, especially canonical TRP channel subfamily members 3 (TRPC3) and 6 (TRPC6), have gained attention as a putative therapeutic target of heart 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 have recently shown that the formation of a protein signal complex between TRPC3 and NADPH oxidase (Nox) 2 caused by environmental stresses (e.g., hypoxia, nutritional deficiency, and anti-cancer 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.
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.
Keywords: TRPC3, TRPC6, Nox2, oncocardiology, protein–protein interaction, drug repurposing.
Graphical Abstract
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