Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet.
BACKGROUND
Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function.


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.
Huang
Y
Y
Department of Surgery, Thomas Jefferson University College of Medicine, Philadelphia, Pa 19107, USA.
Walker
K E
KE
Hanley
F
F
Narula
J
J
Houser
S R
SR
Tulenko
T N
TN
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D003971:Diastole; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D002784:Cholesterol; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases