Human apolipoprotein A-II reduces atherosclerosis in knock-in rabbits

Area of Science:

• Lipid metabolism and cardiovascular research.

Background:

• Apolipoprotein A-II (apoAII) is a major component of high-density lipoprotein (HDL), but its functions are not well understood.
• The specific roles of apoAII in lipoprotein metabolism and atherosclerosis require further investigation.

Purpose of the Study:

• To elucidate the specific functions of apoAII in lipoprotein metabolism and atherosclerosis.
• To utilize a novel rabbit model for studying apoAII's independent effects, separate from apoAI.

Main Methods:

• Generated apoAII knock-in (KI) rabbits using TALEN technology, replacing endogenous apoAI with human apoAII.
• Confirmed exclusive apoAII expression in KI rabbits via RT-PCR and Western blotting.
• Compared lipid profiles, lipoprotein lipase activity, and atherosclerosis development between apoAII KI and wild-type (WT) rabbits.

Main Results:

• ApoAII KI rabbits showed significantly lower plasma triglycerides (52%) and higher HDL-C (28%) compared to WT rabbits.
• KI rabbits exhibited accelerated clearance of triglyceride-rich particles and increased lipoprotein lipase activity.
• ApoAII KI rabbits were resistant to diet-induced hypertriglyceridemia and developed significantly less aortic atherosclerosis.

Conclusions:

• ApoAII plays a protective role against atherosclerosis, potentially by increasing HDL-C and reducing triglycerides.
• ApoAII may represent a novel therapeutic target for managing atherosclerosis and related cardiovascular diseases.