Biphasic alterations in coronary smooth muscle Ca2+ regulation in a repeat cross-sectional study of coronary artery disease severity in metabolic syndrome

Mikaela L. McKenney-Drake, Stacey D. Rodenbeck, Meredith K. Owen, Kyle A. Schultz, Mouhamad Alloosh, Johnathan Tune, Michael Sturek

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and aims: Coronary artery disease (CAD) is progressive, classified by stages of severity. Alterations in Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ in CSM cells revealed heightened Ca2+ 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 Ca2+ regulation and decreased proliferation compared to CSM from the wall. Conclusions: These CSM Ca2+ regulation data from several time points in CAD progression and severity help to resolve the controversy regarding up-vs. down-regulation of CSM Ca2+ regulation in previous reports. These data are consistent with the hypothesis that alterations in sarcoplasmic reticulum Ca2+ contribute to progression of atherosclerotic CAD in MetS.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalAtherosclerosis
Volume249
DOIs
StatePublished - Jun 1 2016

Fingerprint

Smooth Muscle
Coronary Artery Disease
Cross-Sectional Studies
Atherogenic Diet
Fura-2
Smooth Muscle Myocytes
Disease Progression
Sarcoplasmic Reticulum
Atherosclerotic Plaques
Coronary Vessels
Swine
Down-Regulation
Diet

Keywords

  • Calcium regulation
  • Ossabaw swine
  • Proliferation
  • Smooth muscle phenotype

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Biphasic alterations in coronary smooth muscle Ca2+ regulation in a repeat cross-sectional study of coronary artery disease severity in metabolic syndrome. / McKenney-Drake, Mikaela L.; Rodenbeck, Stacey D.; Owen, Meredith K.; Schultz, Kyle A.; Alloosh, Mouhamad; Tune, Johnathan; Sturek, Michael.

In: Atherosclerosis, Vol. 249, 01.06.2016, p. 1-9.

Research output: Contribution to journalArticle

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abstract = "Background and aims: Coronary artery disease (CAD) is progressive, classified by stages of severity. Alterations in Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ in CSM cells revealed heightened Ca2+ 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 Ca2+ regulation and decreased proliferation compared to CSM from the wall. Conclusions: These CSM Ca2+ regulation data from several time points in CAD progression and severity help to resolve the controversy regarding up-vs. down-regulation of CSM Ca2+ regulation in previous reports. These data are consistent with the hypothesis that alterations in sarcoplasmic reticulum Ca2+ contribute to progression of atherosclerotic CAD in MetS.",
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AB - Background and aims: Coronary artery disease (CAD) is progressive, classified by stages of severity. Alterations in Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ in CSM cells revealed heightened Ca2+ 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 Ca2+ regulation and decreased proliferation compared to CSM from the wall. Conclusions: These CSM Ca2+ regulation data from several time points in CAD progression and severity help to resolve the controversy regarding up-vs. down-regulation of CSM Ca2+ regulation in previous reports. These data are consistent with the hypothesis that alterations in sarcoplasmic reticulum Ca2+ contribute to progression of atherosclerotic CAD in MetS.

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