Grape seed proanthocyanidins protect cardiomyocytes from ischemia and reperfusion injury via Akt-NOS signaling

Zuo Hui Shao, Kimberly R. Wojcik, Anar Dossumbekova, Chinwang Hsu, Sangeeta R. Mehendale, Chang Qing Li, Yimin Qin, Willard W. Sharp, Wei Tien Chang, Kimm J. Hamann, Chun Su Yuan, Terry L. Vanden Hoek

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Ischemia/reperfusion (I/R) injury in cardiomyocytes is related to excess reactive oxygen species (ROS) generation and can be modulated by nitric oxide (NO). We have previously shown that grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant, decreased ROS and may potentially stimulate NO production. In this study, we investigated whether GSPE administration at reperfusion was associated with cardioprotection and enhanced NO production in a cardiomyocyte I/R model. GSPE attenuated I/R-induced cell death [18.0 ± 1.8% (GSPE, 50 μg/ml) vs. 42.3 ± 3.0% (I/R control), P < 0.001], restored contractility (6/6 vs. 0/6, respectively), and increased NO release. The NO synthase (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 200 μM) significantly reduced GSPE-induced NO release and its associated cardioprotection [32.7 ± 2.7% (GSPE + L-NAME) vs. 18.0 ± 1.8% (GSPE alone), P < 0.01]. To determine whether GSPE induced NO production was mediated by the Akt-eNOS pathway, we utilized the Akt inhibitor API-2. API-2 (10 μM) abrogated GSPE-induced protection [44.3% ± 2.2% (GSPE + API-2) vs. 27.0% ± 4.3% (GSPE alone), P < 0.01], attenuated the enhanced phosphorylation of Akt at Ser473 in GSPE-treated cells and attenuated GSPE-induced NO increases. Simultaneously blocking NOS activation (L-NAME) and Akt (API-2) resulted in decreased NO levels similar to using each inhibitor independently. These data suggest that in the context of GSPE stimulation, Akt may help activate eNOS, leading to protective levels of NO. GSPE offers an alternative approach to therapeutic cardioprotection against I/R injury and may offer unique opportunities to improve cardiovascular health by enhancing NO production and increasing Akt-eNOS signaling.

Original languageEnglish
Pages (from-to)697-705
Number of pages9
JournalJournal of Cellular Biochemistry
Issue number4
Publication statusPublished - Jul 1 2009
Externally publishedYes


  • Akt
  • Cardiomyocytes
  • Grape seed proanthocyanidin extract
  • Ischemia/reperfusion injury
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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