Effect of metabolic syndrome and aging on Ca 2+ dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine

Jill K. Badin, Rebecca S. Bruning, Michael Sturek

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca 2+ handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca 2+ dysregulation were different in MetS-induced CAD compared to aging-induced CAD. Methods: Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca 2+ ([Ca 2+ ] i ) was assessed with fura-2 imaging. Results: CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca 2+ ] i handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca 2+ store release, increased Ca 2+ influx through voltage-gated Ca 2+ channels, and attenuated sarco-endoplasmic reticulum Ca 2+ ATPase activity. MetS old and MetS young swine had similar Ca 2+ dysregulation. Conclusions: Ca 2+ dysregulation, mainly the SR Ca 2+ store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca 2+ dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the “aging milieu” potentiates effects of Ca 2+ handling dysfunction in CAD.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalExperimental Gerontology
Volume108
DOIs
StatePublished - Jul 15 2018

Keywords

  • Atherosclerosis
  • Intravascular ultrasound
  • Metabolism
  • Obesity
  • Sarco-endoplasmic reticulum Ca ATPase

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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