FIBRINOGEN DEFICIENCY REDUCES VASCULAR ACCUMULATION OF APOLIPOPROTEIN(A) AND DEVELOPMENT OF ATHEROSCLEROSIS IN APOLIPOPROTEIN(A) TRANSGENICMICE

To test directly whether fibrin(ogen) is a key binding site for apolip oprotein(a) [apo(a)] in vessel walls, apo(a) transgenic mice and fibri nogen knockout mice were crossed to generate fibrin(ogen)-deficient ap o(a) transgenic mice and control mice. In the vessel wall of apo(a) tr ansgenic mice, fibrin(ogen) deposition was found to be essentially col ocalized with focal apo(a) deposition and fatty-streak type atheroscle rotic lesions. Fibrinogen deficiency in apo(a) transgenic mice decreas ed the average accumulation of apo(a) in vessel walls by 78% and the a verage lesion (fatty streak type) development by 81%. Fibrinogen defic iency in wild type mice did not significantly reduce lesion developmen t. Our results suggest that fibrin(ogen) provides one of the major sit es to which apo(a) binds to the vessel wall and participates in the ge neration of atherosclerosis.