Fig. 3

Composite of a fourth Tg53 proximal coronary (≈350 micron) lesion phenotype found at end-stage: thick smooth muscle cell-rich cap, intraplaque hemorrhage, thrombosis, disrupted internal elastic laminae. (A) Abundant α-actin immunostalned smooth muscle cells (red) in plaque cap and media of opposing non-lesion side, in contrast to paucity in lesion-side media. Direction of blood flow (⇯); endothelium (➨); internal elastic lamina (➩). Areas of hemorrhage are detected at the plaque base (boxed) and in subjacent media; bar = 100 microns. (B) High magnification of boxed area in (A) reveals numerous α-actin immunostained smooth muscle cells in the plaque cap; disrupted internal elastic lamina (➩) and intraplaque hemorrhage (red blood cells stained green-brown). Minimal α-actin immunostained smooth muscle cells in the lesion-side media; bar = 25 microns. (C) PTAH + fibrin () is detected in areas of plaque hemorrhage (*); bar = 25 microns; disrupted internal elastic lamina (➩); delipidated extracellular lipid globules are noted. (D) VEGF immunostained macrophage foam cells and endothelial cells; none in lesion cap smooth muscle cells. Neovessels filled with red blood cells surround VEGF(+) macrophage foam cells; disrupted internal elastic lamina (➩); bar = 25 microns; high magnification of boxed area in (F). (E) Angiopoietin-2 immunostained macrophage foam cells are surrounded by neovessels filled with confirmatory red blood cells (*); disrupted internal elastic lamina (➩); high magnification of boxed area in (H); bar = 25 microns. (F and G) High magnification of VEGF immunostained ectatic neovessel endothelium (➨) with confirmatory intraluminal red blood cells; internal elastic lamina (➩); bar = 10 microns. (H) High magnification of angiopoietin-2 immunostained macrophage foam cells with surrounding red blood cell pools (*); bar = 10 microns. (I) MMP-3 immunostained smooth muscle cells (smcs) and macrophage foam cells (➨) in the plaque and media; minimal immunostaining in adventitia; disrupted internal elastic lamina (➩). (J) Minimal TIMP3 immunostaining confined to macrophage foam cells (➨); internal elastic lamina (➩); bar = 20 microns. Note: (ad), adventitia; (cap), plaque cap; (fc), foam cells; (m), media; (my), myocardium; (rbcs), red blood cells; (smcs), smooth muscle cells.