- 作者: Tsai-Yueh Luo; Ming-Jai Su; Yi-Fan Yang; Yen-Bin Liu; Hsiu-Chuan Liang; Chau-Chung Wu; Yuan-Teh Lee
- 作者服務機構: Institute of Pharmacology, Department of Internal Medicine and Dpartment of Primary Care Medicine, Colloge of Medicine, National Taiwan University, Taipei, and Institute of Nuclear Energy Research, Taoyuan, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Although hypercholesterolemia is a well-known risk fac-tor for atherosclerosis, little is known about the effect ofhypercholesterolemia on cardiac contractile function.The objective of this study was to examine the effect ofhypercholesterolemia on myocardial contractility. Fif-teen New Zealand white rabbits were fed standard chow(control group) and another 15 were fed a cholesterol-enriched diet (HC group) for 12 weeks. The contractileresponse of ventricular muscle strips was measured invarious extracellular calcium concentrations and at dif-ferent pacing rates. The whole-cell calcium current re-cording, and mRNA and protein levels of cellular cal-cium-handling proteins were also analyzed. With 2 mMCaz+ and stimulation at 3 Hz, the contractile force of HCstrips was less than that of the controls (3.63 0.20 vs.4.61士0.50 mN,p<0.05). The time to peak tension waslonger for HC strips (93.3土2.16 vs. 82.2士2.81 ms, p<0.05). The peak L-type calcium inward current densitywas slightly higher in HC myocytes but did not reach sta-tistical significance(-14.90士0.94 vs. -12.44士0.84 pA/pF, p=0.15). The mRNA level of sarcoplasmic reticulumCa2+-ATPase (SERCA), normalized to GAPDH, was signif-icantly lower in the HC than that in the control group(2.85士0.14 vs. 7.67士0.67, p<0.05), as was the ryano-dine receptor(RyR;0.42士0.06 vs. 0.71士0.13, p<0.05).The mRNA of the Na+/Ca2+ exchanger(NCX) was statisti-cally higher in the HC group (0.90士0.12 vs. 0.48士0.05,p<0.05). Western blot experiments revealed that proteinexpression of SERCA in the HC strips decreased, but thatof the NCX increased. The protein expression of the dihy-dropyridine receptor was similar between these twogroups. We concluded that hype rcholesterolemia resultsin suppression of the maximal contractile function and ina longer systolic contractile time course. These changesmay partially be mediated through a decrease in SERCAand RyR but an increase in NCX expression.
- 中文關鍵字: --
- 英文關鍵字: --