Abstract 5416: Ablation of TRPV1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy

Abstract

Background We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1), a ligand-gated cation channel expressed in sensory nerves innervating the heart, plays an important role in protecting the heart from ischemia/reperfusion injury. However, the role of TRPV1 in pressure overload-induced hypertrophy of the heart is unknown. Objective - This study tests the hypothesis that TRPV1 protects the heart from pressure overload-induced hypertrophy and functional deterioration using gene-targeted TRPV1-null mutant (TRPV1 −/− ) or wild-type (WT) mice. Methods and Results Four weeks after transverse aortic constriction ( TAC ) in TRPV1 −/− and WT mice, echo cardiography demonstrated that cardiac fractional shortening (FS) and ejection fraction (EF) were suppressed in a greater extent in TRPV1 −/− than WT mice (FS: 14 ± 3% in TRPV1 −/− vs. 18 ± 2% in WT mice, P <0.05; EF: 34 ± 6% in TRPV1 −/− vs. 43 ± 3% mice, P <0.05), while there was no difference in FS and EF in TRPV1 −/− and WT sham-operated mice. The ratio of heart weight to body weight (mg/g) was greater in TRPV1 −/− than in WT mice (7.39±1.34 in TRPV1 −/− vs. 6.26±1.07 in WT mice, P <0.05), and the increase in heart weigh was accompanied by an increase in cardiomyocyte cross-sectional areas in TRPV1 −/− compared to WT mice (248±8.2 in TRPV1 −/− vs 224±8.7 in WT μm 2 , P <0.05). Immunohistochemistry study showed enhanced cellular infiltration and fibrosis in TRPV1 −/− compared to WT mice. Consistently, hydroxyproline assay showed that the collagen level was higher in TRPV1 −/− than WT mice (1.7±0.3 in TRPV1 −/− vs 1.3±0.4 μg/mg dry tissue in WT, P <0.05), and ELISA assay showed that interleukin-6 levels were higher in TRPV1 −/− than in WT mice (14.2±4.6 in TRPV1 −/− vs. 10.6±2.6 pg/mg protein in WT, P <0.05). Conclusions These data show that ablation of TRPV1 results in exaggerated cardiac hypertrophy, fibrosis, and dysfunction induced by pressure overload, which may result from enhanced inflammatory responses in the absence of TRPV1.