Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis

Jason M. Edwards, Zachary P. Neeb, Mouhamad A. Alloosh, Xin Long, Ian N. Bratz, Cassandra R. Peller, James P. Byrd, Sanjay Kumar, Alexander G. Obukhov, Michael Sturek

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Aims Stenting attenuates restenosis, but accelerated coronary artery disease (CAD) adjacent to the stent (peri-stent CAD) remains a concern in metabolic syndrome (MetS). Smooth muscle cell proliferation, a major mechanism of CAD, is mediated partly by myoplasmic Ca2+ dysregulation and store-operated Ca2+ entry (SOCE) via canonical transient receptor potential 1 (TRPC1) channels is proposed to play a key role. Exercise is known to prevent Ca2+ dysregulation in CAD. We tested the hypothesis that MetS increases SOCE and peri-stent CAD and exercise attenuates these events.Methods and results Groups (n = 9 pigs each) were (i) healthy lean Ossabaw swine fed standard chow, (ii) excess calorie atherogenic diet fed (MetS), and (iii) aerobically exercise trained starting after 50 weeks of development of MetS (XMetS). Bare metal stents were placed after 54 weeks on diets, and CAD and SOCE were assessed 4 weeks later. Coronary cells were dispersed proximal to the stent (peri-stent) and from non-stent segments, and fura-2 fluorescence was used to assess SOCE, which was verified by Ni 2+ blockade and insensitivity to nifedipine. XMetS pigs had increased physical work capacity and decreased LDL/HDL (P < 0.05), but no attenuation of robust insulin resistance, glucose intolerance, hypertriglyceridaemia, or hypertension. CAD was greater in peri-stented vs. non-stented artery segments. MetS had the greatest CAD, SOCE, and TRPC1 and STIM1 mRNA and protein expression, which were all attenuated in XMetS.Conclusion This is the first report of the protective effect of exercise on native CAD, peri-stent CAD, SOCE, and molecular expression of TRPC1, STIM1, and Orai1 in MetS.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalCardiovascular research
Volume85
Issue number3
DOIs
StatePublished - Feb 1 2010

Keywords

  • Coronary smooth muscle
  • Intravascular ultrasound
  • Orai1
  • Ossabaw miniature swine
  • STIM1
  • Store-operated calcium channel
  • Transient receptor potential 1 channel

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Fingerprint Dive into the research topics of 'Exercise training decreases store-operated Ca<sup>2+</sup>entry associated with metabolic syndrome and coronary atherosclerosis'. Together they form a unique fingerprint.

  • Cite this