To evaluate the effect of hypercholesterolemia on apoptosis (APOP) & proliferation (PROL) after vascular injury, we examined iliac arteries on 1, 3, 7 & 14 days after balloon injury (N=5 at each time) in rabbits with hypercholesterolemia (HC) and normocholesterolemia (NC).

In media immediately after injury, APOP occurred massively & then decreased (TUNEL index=6.3±1.3 at D1, 0.9± 0.7% at D14). HC did not affect early massive APOP but significantly (p<0.01) increased APOP, 3.3±1.5% at D14. Massive early APOP in media was followed by active PROL (PCNA index=6.0±3.3 at D7, 3.9± 2.8% at D14). HC sustained the high activity of PROL upto D14 (8.9±2.7% at D14)(p<0.01). In intima where cells were scanty initially, PROL activity reached peak at D7 and then decreased (6.4±1.8% at D7, 2.5 ±1.8% at D14). HC significantly (p<0.05) enhanced PROL at D14 (5.8±2.2% at D14). In intima PROL was accompanied by low-grade APOP (1.3±1.1% at D7, 0.3±0.2% at D14). HC significantly (p<0.05) enhanced this low-grade APOP at D14 (0.9±0.4%). These effects of HC on APOP & PROL result in a significantly increased area of intima (0.4±0.2 in HC, 0.2±0.1 in NC) & media (0.5±0.1 in HC, 0.4±0.1 in NC) (p<0.01). Fundamental difference between HC & NC was infiltration of macrophage in HC, which was colocalized with APOP & PROL activities.

Balloon injury induces early massive APOP followed by PROL in media, whereas in intima, it induces active PROL followed by low-grade APOP. Hypercholesterolemia does not affect early massive APOP, but enhances PROL & low-grade APOP at late phase, which results in intimal & medial hyperplasia.