Figure 4.

Schematic diagram of TRPV1 and TRPV4 structure and cardiac fibroblast signalling. (A) Basic structure of alpha subunit of TRPV1. (B) Basic structure of alpha subunit of TRPV4. (A-B) Each TRPV1 and TRPV4 alpha subunit is comprised of six transmembrane-spanning domains (S1–S6), with a pore loop between S5 and S6, ankyrin repeats (AnkR) at the amino terminus, and a TRP-box at the carboxyl terminus. (C) Known TRPV1 and TRPV4 homotetrameric ion channel signalling in cardiac fibroblasts. Capsaicin activates TRPV1 and inhibits Ang II-induced cell proliferation. TRPV1 activation also inhibits isoproterenol-induced cell proliferation, and attenuates isoproterenol-induced ECM synthesis, cell proliferation and myofibroblast differentiation by blocking downregulation of p-Akt, p-eNOS, NO and cGMP. TGF-β activates TRPV4, inducing Ca²⁺ influx and promoting RhoA signalling, upregulation of MRTF-A transcription factor, and myofibroblast differentiation. See main text for details.