Lipoprotein production by the heart: a novel pathway of triglyceride export from cardiomyocytes.
The current knowledge on lipoprotein secretion from the heart is examined in this article. The ability of cells to secrete apolipoprotein B (apo-B) containing lipoproteins depends on expression of the apo-B and microsomal triglyceride transfer protein (MTP) genes. Initially, it was shown that both genes are expressed in cardiac myocytes of mice and humans. Electron microscopy of human cardiac myocytes revealed lipoproteins in the secretory pathway and metabolic labelling studies demonstrated the secretion of LDL-like lipoproteins from minced heart biopsies. To examine the role of lipoprotein formation in the heart, we tested whether overexpression of a human apo-B transgene in the heart affects cardiac triglyceride accumulation. In wild-type mice, diabetes conferred an increase in heart triglycerides. In apo-B transgenic mice, diabetes did not affect heart triglycerides. Also, apo-B overexpression prevents fasting-induced heart triglyceride accumulation, whereas inhibition of MTP expression increases heart triglycerides in mice. In hypoxic human hearts, MTP mRNA expression was negatively associated with triglyceride contents. These findings suggest that lipoprotein formation rates affect cardiac triglyceride stores. The MTP mRNA levels are approximately 2-fold higher in hypoxic compared with normoxic human myocardium and in diabetic compared with non-diabetic mouse hearts. In both hypoxia and diabetes, the delivery of triglycerides to the heart exceeds their utilization for beta-oxidation. Thus, endogenous lipoprotein secretion rates might be upregulated to remove surplus fat from the heart. Diabetes negatively affected indexes of systolic and diastolic function in wild-type mice. However, the diabetogenic effects on the heart were absent or much less pronounced in apo-B transgenic mice. This suggests that accelerated lipoprotein formation by the heart attenuates development of diabetic cardiomyopathy in mice. In conclusion, current evidence suggests that lipoprotein secretion from the heart plays an integrated role in cardiac lipid homeostasis and that it can affect the biomechanical function of the heart.
Nielsen
L B
LB
Department of Clinical Chemistry, Lund University, Lund, Sweden. larsbo@rh.dk
D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D001055:Apolipoproteins B; D014280:Triglycerides