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Influence of age and ischemia on cardiac subsarcolemmal and interfibrillar mitochondria in a novel model of estrogen deficiency (680.6)
Author(s) -
Garvin Alexandra,
Aurigemma Nicole,
Lehtihet Nadia,
Hackenberger Jenna,
Korzick Donna
Publication year - 2014
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.28.1_supplement.680.6
Subject(s) - mptp , mitochondrial permeability transition pore , ischemia , medicine , endocrinology , mitochondrion , estrogen , menopause , programmed cell death , cardiology , apoptosis , biology , disease , microbiology and biotechnology , biochemistry , parkinson's disease
Altered mitochondrial respiration (MR) and calcium retention capacity (CRC) are proposed cardiac cell death mechanisms exacerbated by aging in males. The present study aimed, for the first time, to determine changes in mitochondrial subpopulation function with age and ischemia/reperfusion (I/R) injury in the female heart. A novel model to recapitulate human menopause/age interactions was used in F344 female rats ovariectomized (OVX) at 15mo and studied at 24mo (n=15), vs adult (6mo; n=18). MR and CRC were assessed in isolated subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria following in vivo coronary artery ligation (CAL; 31 min I and 10 min R) or sham. State 3 MR energized by either complex I (CI) or complex II (CII) substrates was selectively reduced by age in SSM (p<0.02), and by I/R in IFM (p<0.05). CRC was less in aged vs. adult IFM with I/R (38%), suggesting earlier mitochondrial permeability transition pore (MPTP) opening. At CI, but not CII, cyclosporine A (CsA) enhanced CRC in adult vs. aged (48%), suggesting reduced protective efficacy with age and MPTP involvement. In contrast to males, our data suggest a sex‐specific phenotype whereby reductions in both SSM and IFM dynamics may play an additive role in the enhanced susceptibility to I/R injury and myocardial infarction in the aged female heart, which remains the leading cause of death in older women. Grant Funding Source : Supported by HL091097, AG044132.