Hypoxic preconditioning protects rat hearts against ischemia–reperfusion injury via the arachidonate12-lipoxygenase/transient receptor potential vanilloid 1 pathway
Hypoxic preconditioning (HPC) protects rat hearts against ischemia–reperfusion (IR) injury. However, the role of transient receptor potential vanilloid 1 (TRPV1) in HPC-mediated cardioprotection remains unknown. TRPV1 is activated by endovanilloid 12( S )-hydroxyeicosatetraenoic acid [12( S )-HETE],...
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Published in | Basic research in cardiology Vol. 109; no. 4; p. 414 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.07.2014
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Hypoxic preconditioning (HPC) protects rat hearts against ischemia–reperfusion (IR) injury. However, the role of transient receptor potential vanilloid 1 (TRPV1) in HPC-mediated cardioprotection remains unknown. TRPV1 is activated by endovanilloid 12(
S
)-hydroxyeicosatetraenoic acid [12(
S
)-HETE], which is synthesized by arachidonate 12-lipoxygenase (ALOX12). Therefore, we examined whether HPC protects the myocardium against IR via the ALOX12/TRPV1 pathway. Compared to hearts of rats kept in room air, the hearts of rats kept in air with 10 % oxygen for 4 weeks had better post-ischemic recovery and less tissue damage when subjected to 30-min global ischemia and 4-h reflow in a Langendorff apparatus. Capsazepine, a specific TRPV1 blocker, administered 5 min before reperfusion markedly attenuated the effects of HPC, confirming that TRPV1 is a downstream effector in HPC-mediated cardioprotection. HPC resulted in the upregulation of ALOX12 and myocardial 12(
S
)-HETE, and prevented IR-induced 12(
S
)-HETE reduction. In addition, sarcolemmal ALOX12 expression in HPC hearts mainly co-localized with TRPV1 expression. Blockade of ALOX12 by cinnamyl-3,4-dihydroxy-α-cyanocinnamate or baicalein abrogated the effects of HPC, baicalein also decreased 12(
S
)-HETE expression. Mimicking HPC by given 12(
S
)-HETE or capsaicin to baicalien-treated hearts enhanced cardiac recovery during reperfusion. The cardiac protein kinase C (PKC) isoforms α, δ, ε, and ζ were preferentially expressed in the sarcolemmal membrane of HPC-treated hearts, indicating their high intrinsic activation state. Capsazepine or co-treatment with baicalein attenuated translocation of PKCα, PKCδ and PKCε, but not that of PKCζ. We conclude that HPC reduces heart susceptibly to IR via ALOX12/TRPV1/PKC pathway, as shown by increased 12(
S
)-HETE expression in HPC hearts. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0300-8428 1435-1803 |
DOI: | 10.1007/s00395-014-0414-0 |