Abstract 3738: Immunolocalization of Fibrin in Early and Late Atherosclerotic Plaques: Implications for Its Role in Coronary Plaque Progression
Activation of the coagulation pathway plays a crucial role in atherosclerotic plaque instability, especially atherothrombosis. The role of fibrin in earlier plaque progression has not been fully studied. Cryosections (n=80) of human coronary arteries were stained immunohistochemically for for fibrin and platelet glycoprotein CD61; macrophage scavenger receptor (MSR, type I SRA), matrix metalloproteinase 9 (MMP-9), and cathepsin S (cathS); red blood cell antigen (glycophorin A, glyA); and CD31. Plaques were chosen to represent a range of lesions (6 adaptive intimal thickening, AIT; 25 pathologic intimal thickening, PIT; 37 fibroatheromas, FA; and 12 thin-cap fibroatheromas, TCFA). Staining intensity for fibrin and CD61 was graded as strong or weak on the endothelial surface, and on a 0 – 4 scare in the necrotic core; intimal neovessels were quantitated by CD31 staining. Surface staining or fibrin increased with advancing plaque type, with essentially no staining in AIT, positivity in 19% of PIT, 53% of early FA, 73% of late FA, and 93% of TCFA. There was a strong correlation with surface fibrin and surface macrophages expressing CD68, MSR, MMP-9, and cathepsin S (all p<.0001) and CD61 indicating surface platelets (p< .0001). Across all plaque types endothelial surface colocalization with fibrin was 40% for macrophages expressing cathepsin S, 40% for MSR, 38% for CD68, 25% for MMP-9, and 21% for CD61. Fibrin staining was generally absent in the intima of AIT and PIT, with strong staining in cores of early FA (2.6 ± 0.3), late FA (2.9 ± 0.3), and TCFA (3.0 ± 0.3). There was a strong correlation between intimal fibrin score and numbers of intimal vasavasorum (p<.0001); in 68% of cores with fibrin staining, there was minimal or no evidence of red cell breakdown as evidenced by glyA staining. We conclude that fibrin colocalizes with surface macrophages that express MSR and MMP-9, and may play a role in intimal macrophage entry in early and late plaques. In later plaques, fibrin in necrotic cores and is present proportional to intraplaque vessels and before red cells, indicating leakage of vessels before frank intraplaque hemorrhage. Fibrin plays a role in macrophage entry into the plaque intimal surface, as well as enlargement of the necrotic core.