Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice

Atherosclerosis involves inflammatory processes between vascular tissues an d hematocytes with a hyperlipidemic background. To examine whether variatio ns of hematocytes constitute one of the genetic components in atheroscleros is, irradiated apolipoprotein E (apoE)-deficient (apoE(-/-)) mice with hype rcholesterolemia and preexisting atherosclerotic lesions were reconstituted with mixed bone marrow cells (BMC) from syngeneic and wild-type (apoE(+/+) ; atheroselerosis-resistant SJL or -susceptible B10.S) mice. Stable mixed a llogeneic chimeras with small amounts of serum apoE were established withou t any detrimental complications. Compared with untreated apoE(-/-) mice or apoE(-/-) mice transplanted with syngeneic BMC alone, significant reduction of the cholesterol level and significant lesion regression were observed i n the mixed chimeras. Furthermore, mixed chimeras given SJL BMC showed mark ed reductions in umbers of lesions compared with those reconstituted with B 10.S BMC, Cholesterol levels in the former SJL chimeras, however, were sign ificantly higher than those in the latter B10.S chimeras. These findings in dicate that the resistance of SJL to atherosclerosis resides in the bone ma rrow-derived cells.