Increased oxysterol contents in diabetic rat hearts: their involvement in diabetic cardiomyopathy.
BACKGROUND
Abnormal lipid metabolism associated with diabetes mellitus has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. Oxysterols, oxidation derivatives of cholesterol, are known to be highly cytotoxic.


OBJECTIVE
To monitor changes in myocardial oxysterols and to assess the effect of probucol, a lipid lowering agent, on myocardial lipids and oxysterols in diabetic rats.


RESULTS
Streptozotocin-induced diabetic rats were divided into two groups; one group was put on a standard diet, and the other a diet containing 1% (weight/weight) probucol for eight weeks. Two oxysterols, 7 beta-hydroxycholesterol and 7-ketocholesterol, were identified in myocardium by capillary gas chromatography. Both 7 beta-hydroxycholesterol and 7-ketocholesterol were significantly increased in diabetic rats (49.9 +/- 9.4 ng/mg dry weight versus 5.8 +/- 1.2 in controls, P < 0.05; and 5.3 +/- 1.2 ng/mg dry weight versus 1.7 +/- 0.1 in controls, P < 0.01, respectively). Probucol reduced not only plasma lipids but also myocardial lipids except for cholesterol and sphingomyelin fractions. However, probucol did not improve insulin deficiency, glucose metabolism or myocardial oxysterol contents.


CONCLUSIONS
This study demonstrated an increase in oxysterols in the myocardium of diabetic rats, suggesting that oxysterols may play a role in the development of diabetic cardiomyopathy. Probucol did not decrease the myocardial oxysterol content at the dose used in this study, suggesting that the increase in oxysterols may not be attributed to high circulating concentrations of lipids, but rather to disturbed myocardial metabolism due to insulin deficiency.
Matsui
H
H
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan. hideom@tsuru.med.nagoya-u.ac.jp
Okumura
K
K
Mukawa
H
H
Hibino
M
M
Toki
Y
Y
Ito
T
T
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000378:metabolism*; D007653:Ketocholesterols / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000924:Anticholesteremic Agents; D006888:Hydroxycholesterols; D007653:Ketocholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C003001:7-ketocholesterol; D011341:Probucol