Abstract 835: Cloning and Characterization of a Novel Apolipoprotein that is Induced by Diabetes in Human Heart
Mechanisms involved in the development of heart failure in obese patients are still under study. Obesity promotes excessive deposition of fat in adipose and non adipose tissues. Intramyocardial lipid overload is a relatively common finding in non-ischemic heart failure, especially in obese and diabetic patients, and promotes lipoapoptosis that contributes to the alteration of cardiac function. Lipoprotein production has been proposed as a heart -protective mechanism through the unloading of surplus cellular lipids. Sequence analysis of the differentially expressed genes in obese individuals identified a new apolipoprotein, regulated by obesity in heart. We detected this new protein in human lipoproteins HDL, LDL and VLDL. We designated it Apolipoprotein O. The apolipoprotein O gene is well conserved among species and expressed in a set of human tissues. Confocal immunofluorescence microscopy colocalized apolipoprotein O and perilipins, a cellular marker of the lipid droplet. Chondroitinase ABC deglycosylation analysis or cell incubation with p-nitrophenyl-β-D-xyloside indicated that apolipoprotein O belongs to the proteoglycan family. Naringenin treatment indicated that apolipoprotein O secretion requires microsomal triglyceride transfer protein activity. In addition, we found apolipoprotein O gene expression up-regulated in the human diabetic heart. To our knowledge, apolipoprotein O is the first chondroitine sulfate chain containing apolipoprotein. Apolipoprotein O may be involved in myocardium protective mechanisms against lipid accumulation or it may have specific properties mediated by its unique glycosylation pattern.