Figure 7. Roles of TRPC3-Nox2 complex in myocardial flexibility and plasticity.

(A) Representative LV pressure-volume loops after inferior vena cava occlusion in TRPC3^+/+ and TRPC3^–/– mice. (B and C) Results of LV systolic indexes (end-systolic elastance; E_es) (B) and diastolic indexes (end-diastolic pressure-volume relationship β; EDPVRβ) (C) (n = 5). (D) Cardiac performance under volume overload reflecting the Frank-Starling law in TRPC3^+/+ and TRPC3^–/– mice (n = 6). (E) Cardiac performance under volume overload in C57BL/6J mice treated with Pyr3 (n = 4). (F) Spontaneous walking activity in C57BL/6J mice with and without a running wheel (n = 4). (G–J) Effects of voluntary exercise on heart weight (G) (n = 10), LV performance under volume load (H) (n = 7), and protein abundances of TRPC3, Nox2, HIF1α, and HO-1 (I) (n = 3–4), and relationship between heart weight and Nox2 expression (J). Data are shown as the mean ± SEM. Significance was determined using unpaired t tests in B, C, F, and G and two-way ANOVA followed by Bonferroni’s comparison test in D, E, and H. *P < 0.05, **P < 0.01. (K) Schema for the role of TRPC3 channels in cardiac plasticity. The TRPC3-Nox2 axis restricts volume-loaded LV diastolic filling through ROS production in normal hearts. Increases in the abundance of the TRPC3-Nox2 complex underlie pathological hypertrophy and atrophy. Voluntary exercise can induce physiological hypertrophy under hemodynamic load by reducing the TRPC3-Nox2 complex.