Objective: In rodents scavenger receptor class B type I (SR-BI) is a key molecule for selective uptake of cholesteryl ester from high-density lipoprotein (HDL). This study was aimed to clarify the role of the human SR-BI/CD36 and LIMP-II Analogues-1 (CLA-1) as a molecular target of selective uptake of cholesteryl ester from HDL in vivo.
Methods and results: To clarify the function and regulation of CLA-1 in vivo we produced CLA-1 BAC transgenic mice. In spite of abundant hepatic RNA expression of CLA-1, CLA-1 BAC transgenic mice had no significant effect on mouse HDL cholesterol. Although coexpression of a human scaffolding protein PDZK1 along with CLA-1 enhanced hepatic CLA-1 expression, it did not affect mouse HDL cholesterol levels, either. However, in the presence of human apoA-1, HDL cholesterol level and size were significantly reduced in CLA-1 transgenic mice, and its reduction was more pronounced in CLA-1/human PDZK1 double transgenic mouse.
Conclusions: We established a mouse model to study human reverse cholesterol transport by expressing CLA-1, human PDZK1, and human apoA-I gene. Our results imply that enhancing CLA-1 expression by human PDZK1 in the liver can modulate HDL cholesterol metabolism and possibly enhance reverse cholesterol transport to prevent the progression of atherosclerosis in human.