Mikaela L McKenney-Drake1, Stacey D Rodenbeck2, Meredith K Owen3, Kyle A Schultz2, Mouhamad Alloosh2, Johnathan D Tune2, Michael Sturek4. 1. 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. 2. Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA. 3. 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. 4. Department of Cellular & Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202, USA. Electronic address: msturek@iu.edu.
Abstract
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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: Stacey L Dineen; Mikaela L McKenney; Lauren N Bell; Allison M Fullenkamp; Kyle A Schultz; Mouhamad Alloosh; Naga Chalasani; Michael Sturek Journal: Diabetes Date: 2015-04-06 Impact factor: 9.461
Authors: Mikaela L McKenney-Drake; Stacey D Rodenbeck; Rebecca S Bruning; Ayeeshik Kole; Kyle W Yancey; Mouhamad Alloosh; Harold S Sacks; Michael Sturek Journal: Ann Thorac Surg Date: 2017-02-21 Impact factor: 4.330
Authors: Mikaela L McKenney-Drake; Stacey D Rodenbeck; Meredith K Owen; Kyle A Schultz; Mouhamad Alloosh; Johnathan D Tune; Michael Sturek Journal: Data Brief Date: 2016-04-13
Authors: Jill K Badin; Ayeeshik Kole; Benjamin Stivers; Victor Progar; Anisha Pareddy; Mouhamad Alloosh; Michael Sturek Journal: J Transl Med Date: 2018-03-09 Impact factor: 5.531