Amino terminal 38.9% of apolipoprotein B-100 is sufficient to support cholesterol-rich lipoprotein production and atherosclerosis.

OBJECTIVE Carboxyl terminal truncation of apolipoprotein (apo)B-100 and apoB-48 impairs their capacity for triglyceride transport, but the ability of the resultant truncated apoB to transport cholesterol and to support atherosclerosis has not been adequately studied. The atherogenicity of apoB-38.9 was determined in this study by using our apoB-38.9-only (Apob38.9/38.9) mice. METHODS AND RESULTS ApoB-38.9-lipoproteins (Lp-B38.9) circulate at very low levels in Apob38.9/38.9 mice as small LDLs or HDLs. Disruption of apoE gene in these mice caused accumulation of large amounts of betaVLDL-like LpB-38.9 in plasma. These betaVLDL particles were more enriched with cholesteryl esters but poor in triglycerides compared with the apoB-48-betaVLDL of the apoB-wild-type/apoE-null (Apob+/+/Apoe-/-) mice. Likewise, apoB-38.9-VLDL secreted by cultured Apob38.9/38.9 mouse hepatocytes also had higher ratios of total cholesterol to triglycerides than apoB-48-VLDL secreted by the apoB-48-only hepatocytes. Thus, despite its impaired triglyceride-transporting capacity, apoB-38.9 has a relatively intact capacity for cholesterol transport. Spontaneous aortic atherosclerotic lesions were examined in apoB-38.9-only/apoE-null (Apob38.9/38.9/Apoe-/-) mice at ages 9 and 13 months. Extensive lesions were found in the Apob38.9/38.9/Apoe-/- mice as well as in their Apob+/38.9/Apoe-/- and Apob+/+/Apoe-/- littermates. CONCLUSIONS Deleting the C-terminal 20% from apoB-48 does not impair its ability to transport cholesterol and to support atherosclerosis, thus narrowing the "atherogenic region" of apoB.