The effect of hypercholesterolemia on early atherosclerotic lesions initiated by fibrinopeptide B.
Hypercholesterolemia and thrombosis have been implicated as factors in the development of atherosclerosis. Fibrinopeptide B (FPB) is a short chain peptide cleaved from fibrinogen during the production of fibrin. FPB is a known chemoattractant and has been shown to produce experimental atherosclerotic lesions in association with hypercholesterolemia. The present study was designed to examine the role of hypercholesterolemia in this process and to study the time course of the development of these lesions. Twelve New Zealand White rabbits were placed on an atherogenic diet and had suture carrying either FPB, fibrinopeptide A (FPA), or saline (controls) implanted in the adventitia of the femoral arteries and were sacrificed at 14 days. An equal number of animals were left on a standard diet and underwent similar treatment. Eleven animals were treated as the hypercholesterolemic group but were sacrificed at 2, 4, and 7 days. The thickness of the intima was measured adjacent to the suture in the animals sacrificed at 14 days, and the hypercholesterolemic FPB sites were thicker (12.23 mu +/- 6.60) than either hypercholesterolemic FPA (6.06 mu +/- 3.72), saline (4.94 mu +/- 1.42), or the normocholesterolemic FPB (5.99 mu +/- 4.61), FPA (3.89 mu +/- 2.20), or saline (3.97 mu +/- 1.83) (P less than 0.05 for all groups). Transmission electron microscopy of the hypercholesterolemic FPB group showed evidence of macrophages, actively secreting smooth muscle cells with newly deposited elastin, and foam cells by 7 days. We conclude that FPB attracts or stimulates macrophages and smooth muscle cells and that the resultant cellular and extracellular proliferation favors early atherosclerotic lesion formation in the presence of hypercholesterolemia.
Kadowaki, MH; Singh, TM; Zarins, CK; Glagov, S; Meredith, SC
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