ALTERATIONS IN MITOCHONDRIAL MORPHOLOGY WITH AGE-ASSOCIATED ESTROGEN DEFICIENCY AND ISCHEMIA-REPERFUSION INJURY

Open Access
Author:
Aurigemma, Nicole Christine
Graduate Program:
Physiology
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
July 07, 2015
Committee Members:
  • Donna Hope Korzick, Thesis Advisor
Keywords:
  • ischemia
  • reperfusion
  • myocardial infarction
  • estrogen deficiency
  • ovariectomy
  • mitochondrial morphology
Abstract:
Limited research has been conducted to elucidate age-related changes in the female rat heart. Further, no studies to date have analyzed mitochondrial morphology in the aged estrogen (E2)-deficient female rat heart. To examine the mitochondrial morphological alterations associated with age and E2 loss, we studied F334 female rats (n=40) subjected to coronary artery ligation (CAL) to induce ischemia-reperfusion (I/R) injury. In order to offer a more physiological model of estrogen deficiency with aging, we also utilized bilateral ovariectomy (OVX) in a subset of rats at 15 mo to be studied at 22-23 mo (MO OVX, n=16). Both adult and MO OVX rats underwent 31 min ischemia with reperfusion times 10 min, 6 hr, and 24 hr. 7 day reperfusion was studied in a subset of adult (n=2) and ovary-intact aged rats (n=2). Transmission electron microscopy was used to analyze mitochondrial area, density, and circularity. Western blot analysis was conducted on a subset of samples to assess changes in mitochondrial fission and fusion proteins dynamin-related protein 1 (Drp1), mitochondrial fission 1 (Fis1), mitofusin 1 (Mfn1), and optic atrophy 1 (OPA1). Aging with E2 deficiency resulted in smaller, more numerous mitochondria compared to adult. Increases in mitochondrial area and decreases in density were seen in adult and MO OVX within 6 hr of reperfusion, while reperfusion over 24 hr seemed to indicate recovery from ischemic injury, as mitochondrial areas returned to baseline in adult hearts. Mitochondrial Drp1 significantly increased with I/R, while no significant changes were seen in Fis1, Mfn1 or OPA1. For the first time, our mitochondrial morphological data suggests a temporal resolution for I/R injury in the female rat heart.