Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury Is Blunted by Diet-Induced Obesity

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Author(s): Beihua Zhong, Shuangtao Ma*, Donna H. Wang.

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)

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Background: Activation of transient receptor potential vanilloid subtype 1 (TRPV1) channels protects the heart from ischemia/reperfusion (I/R) injury through releasing calcitonin gene-related peptide (CGRP) and substance P (SP). The current study aimed to study the cardioprotective effects of TRPV1 in obesity.

Methods: TRPV1 gene knockout (TRPV1-/-) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet or for 20 weeks, and then the hearts were collected for I/R injury ex vivo. The hearts were mounted on a Langendorff apparatus and subjected to ischemia (30 min) and reperfusion (40 min) after incubated with capsaicin (10 nmol/L), CGRP (0.1 µmol/L), and SP (0.1 µmol/L). Then, coronary flow, left ventricular peak positive dP/dt (+dP/dt), left ventricular developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP) were measured.

Results: HFD intake remarkably reduced CF, +dP/dt, and LVDP and elevated LVEDP in both strains (P<0.05). Treatment with capsaicin decreased infarct size, increased CF, +dP/dt, and LVDP, and decreased LVEDP in WT mice on control diet (P<0.05), but did not do so in other three groups. Treatment with CGRP and SP decreased infarct size in both strains fed with control diet (P<0.05). In contrast, not all the parameters of cardiac postischemic recovery in HFD-fed WT and TRPV1-/- mice were improved by CGRP and SP.

Conclusions: These results suggest that HFD intake impairs cardiac postischemic recovery. HFD-induced impairment of recovery is alleviated by CGRP in both strains and by SP only in TRPV1-/- mice, indicating that the effects of CGRP and SP are differentially regulated during HFD intake.

Keywords: TRPV1, obesity, ischemia/reperfusion injury, CGRP, substance P

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(E-pub Ahead of Print)
DOI: 10.2174/1871529X19666190912152041
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