Apoptosis and angiogenesis are induced in the unstable coronary atherosclerotic plaque

Objective Apoptosis and angiogenesis may be involved in the pathogenesis of atherosclerosis and plaque destabilization. In this study, we investigated if apoptosis and angiogenesis were induced in the unstable human coronary atherosclerotic plaque compared to stable atherosclerotic plaque. Methods Atherosclerotic plaques from patients with stable (n = 9) and unstable angina (n = 13) were obtained by directional coronary atherectomy performed during percutaneous transluminal coronary angioplasty. Apoptosis was detected by terminal deoxynucleotidyl transferase end labelling (TUNEL), as well as by immunostaining for caspase 3, Bax and Bcl-2. Neovascularization was determined by immunostaining for the endothelial cell-specific CD31, vascular endothelial growth factor (VEGF-A), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), hypoxia inducible factor-1 alpha (HIF-alpha), and the sections were quantified blindly. Results The apoptotic nuclei were more frequently found in the unstable coronary atherosclerotic plaques. When the number of apoptotic cells was quantified, an increased apoptotic index was found in the unstable plaques (P = 0.04). The positive staining for caspase-3 was increased in the unstable plaques (P = 0.0008), while no difference in either Bax or Bcl-2 was found between groups. Neovascularization, as evidenced by lumens surrounded by a CD31 positive endothelial layer, was more frequently present in the plaques from patients with unstable angina (P = 0.04). The number of cells with positive staining for VEGF-A was increased in unstable plaques (P = 0.005). No difference of Ang I, Ang II, HIF1-alpha was found between groups. Conclusions In unstable human coronary plaques, apoptosis probably involving caspase 3 was found. The plaques had an increased neovascularization, probably induced by VEGF-A. These factors may contribute to explaining plaque destabilization and intraplaque haemorrhage. (c) 2005 Lippincott Williams & Wilkins.