HYPERCHOLESTEROLEMIA EXACERBATES TRANSPLANT ARTERIOSCLEROSIS VIA INCREASED NEOINTIMAL SMOOTH-MUSCLE CELL ACCUMULATION - STUDIES IN APOLIPOPROTEIN-E KNOCKOUT MICE

Background Hypercholesterolemia is thought to be a significant risk fa ctor for coronary vasculopathy in cardiac transplant recipients. Metho ds and Results. We examined the development of arteriosclerosis in mou se carotid artery loops allografted from B.10A(2R) (H-2(h2)) donors to normocholesterolemic C57BL/6J (H-2(b)) recipients and hypercholestero lemic C57BL/6J recipients in which the apolipoprotein (apo) E gene had been knocked out. Luminal occlusion and cross-sectional neointimal ar ea were greater in arteries allografted into hypercholesterolemic reci pients at 15 and 30 days after transplantation. We also measured cellu lar and extracellular matrix components of the neointima by computeriz ed planimetry of the fractional areas subtended by smooth muscle cells (anti-alpha-actin stain), collagen (Masson's trichrome), lipid (oil r ed O), and leukocytes (anti-CD45). The neointimal area stained for smo oth muscle cells was significantly greater in hypercholesterolemic rec ipients than in normocholesterolemic recipients at 15 and 30 days afte r allografting. Lipid contributed to neointimal area to a lesser degre e, and there was no significant increase in the contribution of collag en or leukocytes. Conclusions Smooth muscle cell accumulation appears to be the principal contributor to the increase in neointimal area obs erved in arteries allografted into hypercholesterolemic mice.