2001/11/01 by Francisco Blanco‐Vaca, Joan Carles Escolá‐Gil, Jesús M. Martín‐Campos +1 · 3 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Chemistry · #Peroxisome Proliferator-Activated Receptors #Diabetes, Cardiovascular Risks, and Lipoproteins #Cancer, Lipids, and Metabolism #Apolipoprotein B #Very low-density lipoprotein #Genetically modified mouse #Transgene #Cholesterol #Endocrinology #Internal medicine #Apolipoprotein E #Biology #Lipoprotein #Catabolism #Lipid metabolism #Metabolism #Chemistry #Gene #Biochemistry #Disease #Medicine
paper · pdf · doi:10.1016/s0022-2275(20)31499-1
openalex publication_date 2001/11/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Our understanding of apolipoprotein A-II (apoA-II) physiology is much more limited than that of apoA-I. However, important and rather surprising advances have been produced, mainly through analysis of genetically modified mice. These results reveal a positive association of apoA-II with FFA and VLDL triglyceride plasma concentrations; however, whether this is due to increased VLDL synthesis or to decreased VLDL catabolism remains a matter of controversy. As apoA-II-deficient mice present a phenotype of insulin hypersensitivity, a function of apoA-II in regulating FFA metabolism seems likely. Studies of human beings have shown the apoA-II locus to be a determinant of FFA plasma levels, and several genome-wide searches of different populations with type 2 diabetes have found linkage to an apoA-II intragenic marker, making apoA-II an attractive candidate gene for this disease. The increased concentration of apoB-containing lipoproteins present in apoA-II transgenic mice explains, in part, why these animals present increased atherosclerosis susceptibility. In addition, apoA-II transgenic mice also present impairment of two major HDL antiatherogenic functions: reverse cholesterol transport and protection of LDL oxidative modification. The apoA-II locus has also been suggested as an important genetic determinant of HDL cholesterol concentration, even though there is a major species-specific difference between the effects of mouse and human apoA-II. As antagonizing apoA-I antiatherogenic actions can hardly be considered the apoA-II function in HDL, this remains a topic for future investigations. We suggest that the existence of apoA-II or apoA-I in HDL could be an important signal for specific interaction with HDL receptors such as cubilin or heat shock protein 60.