Apolipoprotein A2 reduces the levels of circulating triglyceride-rich lipoproteins, an effect blocked by apolipoprotein E

Apolipoprotein A2 (APOA2), the second in quantity apolipoprotein of high density lipoprotein (HDL) is synthesized by the liver and much less by the intestine. Studies in humans, failed to establish a clear role for APOA2 in coronary heart disease and overall human physiology. Even though we know that APOA2 plays a key role in the biogenesis and functionality of HDL particles and can interact physically with other apolipoproteins such as apolipoprotein E (APOE), forming dimers, our knowledge on its role in triglyceride-rich lipoprotein (TRL) metabolism remains limited. Here, we investigated how functional interactions between APOA2 and APOE may affect plasma lipoprotein metabolism in the absence of apolipoprotein A1 (APOA1). For this purpose, APOA1 deficient and APOA1xAPOE double deficient mice were fed high fat diet for two weeks and were subsequently infected with either an adenovirus expressing the human APOA2 (AdAPOA2) or a control adenovirus AdGFP. Five days post-infection blood was collected, and plasma and lipoprotein fractions were isolated. After confirmation of human APOA2 expression in vivo by western blot we measured plasma and lipoprotein total cholesterol and triglyceride levels. APOA2 expression increased total cholesterol and triglyceride levels in APOA1 deficient mice. To the contrary, when APOA2 was expressed in APOA1xAPOE double deficient mice, which lack functional APOE a significant reduction in both plasma cholesterol and triglyceride levels associated with a notable reduction in TRL was observed. Overall, our data support that a significant functional interaction between APOA2 and APOE impacts plasma TRL metabolism.