期刊
CELLS
卷 9, 期 8, 页码 -出版社
MDPI
DOI: 10.3390/cells9081770
关键词
sphingosine-1-phosphate; ischemia; reperfusion; cardioprotection; vasoconstriction; coronary flow; myocardial function; myocardial infarct; albumin
类别
资金
- Hungarian National Research, Development and Innovation Office [K-112964, K-125174, NVKP_16-1-2016-0042]
- Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary
- [EFOP-3.6.3-VEKOP-16-2017-00009]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK056014, ZIADK056015] Funding Source: NIH RePORTER
Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator with diverse biological function mediated by S1P(1-5)receptors. Whereas S1P was shown to protect the heart against ischemia/reperfusion (I/R) injury, other studies highlighted its vasoconstrictor effects. We aimed to separate the beneficial and potentially deleterious cardiac effects of S1P during I/R and identify the signaling pathways involved. Wild type (WT), S1P(2)-KO and S1P(3)-KO Langendorff-perfused murine hearts were exposed to intravascular S1P, I/R, or both. S1P induced a 45% decrease of coronary flow (CF) in WT-hearts. The presence of S1P-chaperon albumin did not modify this effect. CF reduction diminished in S1P(3)-KO but not in S1P(2)-KO hearts, indicating that in our model S1P(3)mediates coronary vasoconstriction. In I/R experiments, S1P(3)deficiency had no influence on postischemic CF but diminished functional recovery and increased infarct size, indicating a cardioprotective effect of S1P(3). Preischemic S1P exposure resulted in a substantial reduction of postischemic CF and cardiac performance and increased the infarcted area. Although S1P(3)deficiency increased postischemic CF, this failed to improve cardiac performance. These results indicate a dual role of S1P(3)involving a direct protective action on the myocardium and a cardiosuppressive effect due to coronary vasoconstriction. In acute coronary syndrome when S1P may be released abundantly, intravascular and myocardial S1P production might have competing influences on myocardial function via activation of S1P(3)receptors.
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