Factors stimulating collagen synthesis from the livers of hypercholesterolemic rats

Hypercholesterolemia was induced in rats by feeding them a high cholesterol olive oil diet. The livers were homogenized in modified Krebs-Ringer medium and centrifuged at 35,000 x g. The supernatants from livers of both hypercholesterolemic and normal rats were found to stimulate collagen synthesis in freshly isolated embryonic chick-tendon fibroblasts. However, this was significantly greater in the supernatants from fatty livers. The stimulating principle proceed to be dialyzable, non-lipid and heat-stable. There were at least two factors involved, the more effective of which was trypsin-sensitive, with a molecular weight below 2,000. The results suggest that a mediator is formed in the livers of hypercholesterolemic rats which might be responsible for the enhanced collagen synthesis of fibrotic processes vivo, e.g., in atherosclerosis and liver cirrhosis.