title: Biphasic alterations in coronary smooth muscle Ca(2+) regulation in a repeat cross-sectional study of coronary artery disease severity in metabolic syndrome.
abstract: Coronary artery disease (CAD) is progressive, classified by stages of severity. Alterations in Ca(2+) regulation within coronary smooth muscle (CSM) cells in metabolic syndrome (MetS) have been observed, but there is a lack of data in relatively early (mild) and late (severe) stages of CAD. The current study examined alterations in CSM Ca(2+) regulation at several time points during CAD progression.
  
  
  
  MetS was induced by feeding an excess calorie atherogenic diet for 6, 9, or 12 months and compared to age-matched lean controls. CAD was measured with intravascular ultrasound (IVUS). Intracellular Ca(2+) was assessed with fura-2.
  
  
  
  IVUS revealed that the extent of atherosclerotic CAD correlated with the duration on atherogenic diet. Fura-2 imaging of intracellular Ca(2+) in CSM cells revealed heightened Ca(2+) signaling at 9 months on diet, compared to 6 and 12 months, and to age-matched lean controls. Isolated coronary artery rings from swine fed for 9 months followed the same pattern, developing greater tension to depolarization, compared to 6 and 12 months (6 months = 1.8 ± 0.6 g, 9 months = 5.0 ± 1.0 g, 12 months = 0.7 ± 0.1 g). CSM in severe atherosclerotic plaques showed dampened Ca(2+) regulation and decreased proliferation compared to CSM from the wall.
  
  
  
  These CSM Ca(2+) regulation data from several time points in CAD progression and severity help to resolve the controversy regarding up-vs. down-regulation of CSM Ca(2+) regulation in previous reports. These data are consistent with the hypothesis that alterations in sarcoplasmic reticulum Ca(2+) contribute to progression of atherosclerotic CAD in MetS.
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA; College of Pharmacy & Health Sciences, Butler University, 4600 Sunset Ave., Indianapolis, IN 46208, USA.
authors.forename: Mikaela L
authors.initials: ML
authors.lastname: McKenney-Drake
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA.
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Rodenbeck
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA; Covance, Inc., 671 South Meridian Road, Greenfield, IN 46140, USA.
authors.forename: Meredith K
authors.initials: MK
authors.lastname: Owen
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Schultz
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA.
authors.forename: Mouhamad
authors.initials: M
authors.lastname: Alloosh
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA.
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA. Electronic address: msturek@iu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
mesh_terms: D000818:Animals; D001158:Arteries / Q000000981:diagnostic imaging; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D018450:Disease Progression; D024821:Metabolic Syndrome / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010641:Phenotype; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature
chemical_list: D015220:Calcium Channels; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: Calcium regulation; Ossabaw swine; Proliferation; Smooth muscle phenotype