Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet

被引:96
作者
Huang, Y
Walker, KE
Hanley, F
Narula, J
Houser, SR
Tulenko, TN
机构
[1] Thomas Jefferson Univ, Sch Med, Dept Surg, Coll Med, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Coll Med, Dept Biochem, Philadelphia, PA 19107 USA
[3] Thomas Jefferson Univ, Coll Med, Dept Mol Pharmacol, Philadelphia, PA 19107 USA
[4] Temple Univ, Sch Med, Dept Physiol, Philadelphia, PA 19122 USA
[5] Med Coll Penn & Hahnemann Univ, Sch Med, Dept Med, Div Cardiol, Philadelphia, PA 19102 USA
[6] Coll Allied Hlth Profess, Philadelphia, PA USA
关键词
heart failure; cardiomyopathy; myosin; sarcoplasmic reticulum; hypercholesterolemia;
D O I
10.1161/01.CIR.0000109213.10461.F6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background - Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function. Methods and Results - We examined the effects of cholesterol feeding (0.5%) on cardiac function in rabbits. After 10 weeks, both systolic shortening and diastolic relaxation rates were impaired without any change in aortic pressure or ventricular hypertrophy. However, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)- 2 mRNA levels were reduced within 4 days after initiation of cholesterol feeding. After this effect, SERCA-2 protein and SERCA-mediated Ca uptake into sarcoplasmic reticulum vesicles were impaired, and the ratio of MHC-beta to MHC-alpha mRNA increased 5-fold. Suppression of the SERCA-2 message correlated temporally with enrichment of the cardiac sarcolemma with cholesterol. Conclusions - These data demonstrate that dietary hypercholesterolemia induces a "cholesterol cardiomyopathy" characterized by systolic and diastolic dysfunction. These alterations were independent of vascular disease and demonstrate a dietary link to cardiac dysfunction.
引用
收藏
页码:97 / 102
页数:6
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