Expression of lipoprotein lipase on the surface of cardiomyocytes in transgenic mice increased cardiac lipid uptake and produced a dilated cardiomyopathy with impaired systolic function.
Does lipoprotein lipase expressed on the surface of cardiomyocytes increase lipid uptake and produce cardiomyopathy in transgenic mice?
Expression of lipoprotein lipase on the surface of cardiomyocytes is sufficient to increase lipid uptake and induce cardiomyopathy in a transgenic mouse model.
Absolute Event Rate: 0.33% vs 0.58%
p-value: p=<0.01
Lipoprotein lipase is the principal enzyme that hydrolyzes circulating triglycerides and liberates free fatty acids that can be used as energy by cardiac muscle. Although lipoprotein lipase is expressed by and is found on the surface of cardiomyocytes, its transfer to the luminal surface of endothelial cells is thought to be required for lipoprotein lipase actions. To study whether nontransferable lipoprotein lipase has physiological actions, we placed an alpha-myosin heavy-chain promoter upstream of a human lipoprotein lipase minigene construct with a glycosylphosphatidylinositol anchoring sequence on the carboxyl terminal region. Hearts of transgenic mice expressed the altered lipoprotein lipase, and the protein localized to the surface of cardiomyocytes. Hearts, but not postheparin plasma, of these mice contained human lipoprotein lipase activity. More lipid accumulated in hearts expressing the transgene; the myocytes were enlarged and exhibited abnormal architecture. Hearts of transgenic mice were dilated, and left ventricular systolic function was impaired. Thus, lipoprotein lipase expressed on the surface of cardiomyocytes can increase lipid uptake and produce cardiomyopathy.
Yagyu et al. (Sat,) conducted a other in Cardiomyopathy. hLpLGPI transgene expression vs. LpL1 (heterozygous LpL knockout) mice was evaluated on Fractional shortening (p=<0.01). Expression of lipoprotein lipase on the surface of cardiomyocytes in transgenic mice increased cardiac lipid uptake and produced a dilated cardiomyopathy with impaired systolic function.