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

Abstract

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 (CF), 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.

CONCLUSION

These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced 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.

Authors+Show Affiliations

Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, 788 Service Rd, East Lansing, MI 48824, United States.Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, 788 Service Rd, East Lansing, MI 48824, United States.Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, 788 Service Rd, East Lansing, MI 48824, United States. Neuroscience Program, Michigan State University, 788 Service Rd, East Lansing, MI 48824, United States. Cell & Molecular Biology Program, Michigan State University, 788 Service Rd, East Lansing, MI 48824, United States.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31513001

Citation

Zhong, Beihua, et al. "Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury Is Blunted By Diet-Induced Obesity." Cardiovascular & Hematological Disorders Drug Targets, vol. 20, no. 2, 2020, pp. 122-130.
Zhong B, Ma S, Wang DH. Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity. Cardiovasc Hematol Disord Drug Targets. 2020;20(2):122-130.
Zhong, B., Ma, S., & Wang, D. H. (2020). Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity. Cardiovascular & Hematological Disorders Drug Targets, 20(2), 122-130. https://doi.org/10.2174/1871529X19666190912152041
Zhong B, Ma S, Wang DH. Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury Is Blunted By Diet-Induced Obesity. Cardiovasc Hematol Disord Drug Targets. 2020;20(2):122-130. PubMed PMID: 31513001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effects of TRPV1 Activation Against Cardiac Ischemia/ Reperfusion Injury is Blunted by Diet-Induced Obesity. AU - Zhong,Beihua, AU - Ma,Shuangtao, AU - Wang,Donna H, PY - 2019/06/08/received PY - 2019/06/12/revised PY - 2019/07/17/accepted PY - 2019/9/13/pubmed PY - 2021/3/23/medline PY - 2019/9/13/entrez KW - CGRP KW - TRPV1 KW - congestive heart failure KW - ischemia/reperfusion injury KW - obesity KW - substance P. SP - 122 EP - 130 JF - Cardiovascular & hematological disorders drug targets JO - Cardiovasc Hematol Disord Drug Targets VL - 20 IS - 2 N2 - 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 (CF), 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. CONCLUSION: These results suggest that HFD intake impairs cardiac postischemic recovery. HFDinduced 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. SN - 2212-4063 UR - https://www.unboundmedicine.com/medline/citation/31513001/Protective_Effects_of_TRPV1_Activation_Against_Cardiac_Ischemia/_Reperfusion_Injury_is_Blunted_by_Diet_Induced_Obesity_ L2 - http://www.eurekaselect.com/174835/article DB - PRIME DP - Unbound Medicine ER -