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Local Delivery of an PKCε‐Activating Peptide Improves Ischemic Tolerance in Estrogen Deficient and Aged Rats and Regulates Protective Gene Expression
Author(s) -
Jefferson Sarah Jane,
Lancaster Timothy S,
Tomicek Nanette J,
Korzick Donna H
Publication year - 2008
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.22.1_supplement.750.22
Subject(s) - cardioprotection , estrogen , medicine , protein kinase c , endocrinology , activator (genetics) , enos , ischemia , cardiology , andrology , biology , kinase , nitric oxide , microbiology and biotechnology , nitric oxide synthase , receptor
Background: Age is a leading and poorly understood risk factor for the development of acute coronary syndrome in post‐menopausal women. The failed efficacy of estrogen (E 2 ) replacement to confer cardioprotection has spurred interest to identify alternative therapeutic targets. In aged male hearts, selective PKCε activation limits ischemia‐reperfusion (I/R) damage; however, whether acute PKCε activation is sufficient to produce a protected phenotype in aged females is unknown. Purpose: To determine whether local delivery of an PKCε‐activator peptide (ψ∈RACK) reduces I/R damage in aged and E 2 ‐deficient (OVX) female hearts. Methods: LV contractile responses were assessed in Langendorff‐perfused hearts (5 mmHg EDP, 260 bpm, 85 mmHg) from gonad intact and OVX, adult (5–6 mo) and aged (24 mo) F344 rats (n=5–7/group). Prior to I (47 min), hearts were perfused with either Tat‐ψ∈RACK (500 nM) or Tat (500 nM) for 10 min. Infarct size was assessed using triphenyltetrazolium staining and gene transcription through real time PCR (RACK2, CX43 and eNOS). Results: Recovery of LV developed pressure was significantly improved and infarct size reduced by ψεRACK in aged intact and OVX vs age‐matched controls (60% & 80% vs 21% & 33%; p<0.05). RACK2 mRNA was increased in aged but not adult (p<0.05). Conclusions: Our results suggest, for the first time, a central role for PKCε as a potential target to limit I/R damage with aging in females.