Comparison of Proliferative Activity in Coronary Plaques from Patients with Coronary Ischemia

The overgrowth of cells of the vessel wall, especially of the smooth muscle cells (SMCs), contributes to the pathogenesis of coronary atherosclerosis and wound repair after coronary angioplasty. However, the association between cellular proliferation in coronary lesions and clinical pathophysiology remains to be clarified in humans. Thus, we investigated proliferative activity in coronary tissues obtained from patients with coronary ischemia. The proliferative activity in tissues obtained by using directional coronary atherectomy (DCA) from 87 coronary lesions was assessed by immunohistochemical staining for the proliferating cell nuclear antigen (PCNA). The lesions were divided into 34 primary lesions and 53 postangioplasty lesions. The 34 primary tissue samples were obtained from 9 patients with stable angina pectoris (SAP) and 25 patients with acute coronary syndromes (ACS). Collectively, the 53 postangioplasty tissue samples were obtained from 37 patients with SAP and 16 patients with ACS. The PCNA labeling index (LI) was quantified as the mean percentage of PCNA-positive cells in the 3 most positive high-power fields (×200). The mean Lis were high in the primary ACS samples [8.9 ± 2.1 % (p=0.01)] and postangioplasty samples [2.3 ± 0.8% (p=0.08) in SAP cases and 4.1 ± 2.4% (p=0.06) in ACS cases] compared with the primary SAP samples (0.2 ± 0.2%). Intimal hyperplasia, a random proliferation of SMCs (a-actin positive) was marked in the primary ACS samples (76%) as well as in the postangioplasty SAP (92%) and ACS (81 %) samples, as compared with the primary SAP samples (33%) (p<0.01). PCNA expression was mainly evident in the nucleus of the SMCs and CD68-positive macrophages. Many PCNA-positive cells were localized in plaque areas, as follows: intimal hyperplasia, neovascularized lesions, lesions with macrophage clusters, and lesions near areas of disrupted internal elastic lamina. The levels of PCNA expression in coronary lesions were not associated with the subsequent development of restenosis after DCA. Our findings suggest that the excessive proliferation of vascular wall cells, especially SMCs, is involved in the pathogenesis of ACS and in the process of wound repair after angioplasty in humans.