Increased calcium buffering in coronary smooth muscle cells from diabetic dyslipidemic pigs

Brent J.F. Hill, Elmer M. Price, Joseph L. Dixon, Michael Sturek

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

No studies exist concerning the ability of the plasma membrane Ca2+ pump (PMCA), sarcoplasmic reticulum Ca2+ pump (SERCA) and Na+-Ca2+ exchanger (NCX) to regulate myoplasmic Ca2+ (Cam) in vascular smooth muscle cells from diabetic individuals with dyslipidemia. We tested the hypothesis that diabetic dyslipidemia would increase vascular smooth muscle cells to buffer Cam. Cells were isolated from the coronary artery of male Yucatan pigs treated for 20 weeks with: (1) a low fat diet (control group); (2) a high fat/cholesterol diet (F group); or (3) alloxan-induced diabetic pigs fed the high fat diet (DF group). The maximum Cam response to a depolarizing 80 mM KCl (80 K) solution was evaluated in the absence and presence of thapsigargin (TSG; inhibits SERCA) and low Na (inhibits NCX). In response to 80 K alone, there was no difference in the Cam response between groups. In the presence of TSG, the 80 K response decreased by 43% in the DF group; TSG did not affect the 80 K response in the control and F groups. When exposed to both TSG and low Na, the 80 K response also decreased by 55% in the DF group. This suggests increased Cam buffering by the PMCA and/or mitochondria in the DF group when SERCA and NCX are inhibited. Compared to the control and F groups, low Na alone elicited a 50% lower Cam amplitude in the DF group, which was reversed with TSG treatment; this suggests that SERCA activity is increased in DF pigs. Western blots also indicated a 7-fold increase in the ≃115 kDa band density of an anti-SERCA2 antibody in DF compared to control pigs. This is the first report to demonstrate increased Ca2+ buffering, specifically by SERCA, in vascular smooth muscle cells from diabetic individuals with dyslipidemia.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalAtherosclerosis
Volume167
Issue number1
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

Keywords

  • Artery
  • Atherosclerosis
  • Calcium
  • Diabetes
  • Plasma membrane Ca pump
  • Sarcoplasmic reticulum Ca pump

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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