Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement

In a histopathologic study, we assessed the balance of cell proliferation and apoptosis by counting the number of apoptotic and proliferating cell nuclear antigen-positive cells in freshly harvested atherectomy specimens from 34 patients.

Remodeling of human coronary arteries is an adaptive process that alters vascular lumen size.

Intravascular ultrasound was performed prior to atherectomy. Total vessel area (area within the external elastic lamina [EEL]), lumen area and plaque area were measured at the region of interest (ROI), and at a proximal and distal reference segment, utilizing the formula Delta(%)=100x(ROI-reference segment)/reference segment. Positive arterial remodeling (R+) resulting in luminal expansion was defined as DeltaEEL >10%. Absence of remodeling (0 < DeltaEEL <10%) and constrictive arterial remodeling (DeltaEEL <0) were considered as neutral remodeling (R0) and negative remodeling (R-), respectively.

In R- lesions, apoptotic indices (APO) were significantly elevated (17.17 +/- 2.19%) compared with R+ lesions (4.89 +/- 1.7%; p = 0.0007). In a rabbit iliac percutaneous transluminal coronary angioplasty model intimal apoptosis was increased four weeks after balloon angioplasty injury (APO 8.8 +/- 0.03%) compared with contralateral untreated segments (APO 3.0 +/- 0.04%, n = 6). Lesions with an EEL/intimal area <3.0 showed significantly more intimal apoptosis than untreated lesions (p = 0.02).

The data indicate that constrictive remodeling of atherosclerotic coronary lesions is associated with increased apoptosis of intimal cells. We speculate that increased apoptosis is due to extensive plaque healing after episodes of symptomatic or asymptomatic plaque rupture.