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Determining the mechanism of inhibition of mitochondrial Ca2+ overload by the cocoa flavanol (‐)‐epicatechin as a means of conferring cardioprotection during ischemia‐reperfusion
Author(s) -
Herrera Andrea,
Echeverri Jonathan,
Khan Priya,
Yamazaki Katrina
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.682.13
Subject(s) - cardioprotection , nitric oxide , mitochondrion , soluble guanylyl cyclase , apoptosis , chemistry , ischemia , pharmacology , nitric oxide synthase , biochemistry , medicine , biology , guanylate cyclase , organic chemistry
A diet rich in flavonoids has been shown to have a negative correlation with the incidence of cardiovascular disease. Epicatechin (EPI), a cocoa flavonoid, reduced infarct size and improved long‐term left ventricular structure and function post ischemia reperfusion (IR) by significantly inhibiting mitochondrial calcium (Ca 2+ ) overload, a process that induces apoptosis. However, the mechanism is not known. Our objective is to determine the mechanisms by which EPI inhibits Ca 2+ overload using an in vitro model of simulated IR. We hypothesize that activation of the nitric oxide‐soluble guanylyl cyclase signaling (NO‐sGC) pathway is involved in EPI's protection. Our results demonstrate that EPI significantly decreased Ca 2+ overload by 2.5‐fold and preserved mitochondrial structure by 4‐fold post IR in HL‐1 cardiomyocytes compared to controls. This correlated with a 20% decrease in apoptosis as determined by cell counts. Studies are being conducted to assess mitochondrial respiration and expression of key proteins involved in the NO‐sGC pathway and nitric oxide production. We anticipate that an increase in mitochondrial respiration and nitric oxide production will be observed in EPI treated cells. Taken together, these results will contribute to improving human health by identifying a mechanism of action of an inexpensive and safe dietary supplement that will lead to a simple and economic treatment for CVD's.