Huang Y, Walker K E, Hanley F, Narula J, Houser S R, Tulenko T N
Department of Surgery, Thomas Jefferson University College of Medicine, Philadelphia, Pa 19107, USA.
Circulation. 2004 Jan 6;109(1):97-102. doi: 10.1161/01.CIR.0000109213.10461.F6. Epub 2003 Dec 15.
Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function.
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.
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.
尽管高胆固醇血症是冠状动脉疾病公认的危险因素，但其对心脏功能的直接影响却知之甚少。
我们研究了给予兔子0.5%胆固醇饲料对心脏功能的影响。10周后，收缩期缩短和舒张期松弛率均受损，而主动脉压力或心室肥厚无任何变化。然而，在开始给予胆固醇饲料后4天内，肌浆网/内质网Ca2+-ATP酶（SERCA）-2 mRNA水平降低。在此效应之后，SERCA-2蛋白和SERCA介导的Ca摄取到肌浆网小泡中受损，且MHC-β与MHC-α mRNA的比值增加了5倍。SERCA-2信息的抑制在时间上与心肌细胞膜胆固醇富集相关。
这些数据表明，饮食性高胆固醇血症可诱发以收缩和舒张功能障碍为特征的“胆固醇性心肌病”。这些改变与血管疾病无关，并证明饮食与心脏功能障碍之间存在联系。
