Apolipoprotein A‐II, a Player in Multiple Processes and Diseases

Abstract

Apolipoprotein A‐II (apoA‐II) is the second most abundant apolipoprotein in high‐density lipoprotein (HDL) particles, playing an important role in lipid metabolism. Human and murine apoA‐II proteins have dissimilar properties, partially because human apoA‐II is dimeric whereas the murine homolog is a monomer, suggesting that the role of apoA‐II may be quite different in humans and mice. As a component of HDL, apoA‐II influences lipid metabolism, being directly or indirectly involved in vascular diseases. Clinical and epidemiological studies resulted in conflicting findings regarding the proatherogenic or atheroprotective role of apoA‐II. Human apoA‐II deficiency has little influence on lipoprotein levels with no obvious clinical consequences, while murine apoA‐II deficiency causes HDL deficit in mice. In humans, an increased plasma apoA‐II concentration causes hypertriglyceridemia and lowers HDL levels. This dyslipidemia leads to glucose intol-erance, and the ensuing high blood glucose enhances apoA‐II transcription, generating a vicious circle that may cause type 2 diabetes (T2D). ApoA‐II is also used as a biomarker in various diseases, such as pancreatic cancer. Herein, we provide a review of the most recent findings regarding the roles of apoA‐II and its functions in various physiological processes and disease states, such as cardiovascular disease, cancer, amyloidosis, hepatitis, insulin resistance, obesity, and T2D.