title: Transient Receptor Potential Vanilloid Subtype 1 Inhibits Inflammation and Apoptosis via the Release of Calcitonin Gene-Related Peptide in the Heart after Myocardial Infarction.
abstract: A high mortality rate occurs with silent myocardial infarction (MI), particularly in aging and diabetic populations due to defects in the transient receptor potential vanilloid (TRPV1)-positive sensory nerve function. We have previously shown that TRPV1 deficiency markedly enhances post-MI inflammation and remodeling. However, the mechanisms remain unknown. The objective of this study was to clarify whether calcitonin gene-related peptide (CGRP) release was associated with the protective role of TRPV1 against postmyocardial inflammation and apoptosis.
  
  
  
  TRPV1 gene knockout (TRPV1KO) and wild-type (WT) mice were subjected to left anterior descending ligation or sham operation. The concentration of CGRP in the myocardium was measured at 30 min, 1, 6 and 24 h post-MI. Mice received saline vehicle, CGRP or the CGRP antagonist CGRP8-37 before ligation. Inflammation was evaluated by ELISA assay and histological staining. Apoptosis was assessed by Western blot and TUNEL assay.
  
  
  
  Post-MI, both TRPV1KO and WT mice displayed elevated CGRP levels in myocardium when compared to sham controls. However, the levels of CGRP were significantly lower in TRPV1KO mice than in WT mice at 30 min after MI. Exogenous CGRP downregulated the levels of tumor necrosis factor-α and interleukin-6 expression in TRPV1KO mice post-MI. Moreover, exogenous CGRP decreased the neutrophil infiltration in TRPV1KO mice, whereas inhibition of CGRP by CGRP8-37 increased the neutrophil infiltration in WT mice. Western blotting data indicated that CGRP attenuated caspase-3 and caspase-9 expression, and enhanced Bcl-2 expression in TRPV1KO mice post-MI. CGRP8-37 upregulated caspase-3 and caspase-9 expression and downregulated Bcl-2 expression in WT mice.
  
  
  
  Our data suggest a protective role of TRPV1 activation against inflammation and apoptosis in mice post-MI, possibly through CGRP release. These findings elucidate a neurogenic mechanism in mice post-MI, which may participate in sensory neurotransmitter-mediated protection in TRPV1 activation.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Jiayan
authors.initials: J
authors.lastname: Lei
authors.forename: Fengxi
authors.initials: F
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lixiao
authors.initials: L
authors.lastname: Duan
authors.forename: Han
authors.initials: H
authors.lastname: Lei
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D015536:Down-Regulation; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D065840:Protective Factors; D013565:Sympatholytics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D050916:TRPV Cation Channels / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D010446:Peptide Fragments; D013565:Sympatholytics; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C058636:calcitonin gene-related peptide (8-37); C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9; D015740:Calcitonin Gene-Related Peptide