Effect of Hypercholesterolemia on Cell Proliferation and Apoptosis in Rabbit Iliac Artery after Balloon-injury

Rhee, Moo Yong; Choi, Young Jin; Chae, In Ho; Kim, Hyo Soo; Sohn, Dae Won; Oh, Byung Hee; Lee, Myoung Mook; Park, Young Bae; Choi, Yun Shik; Lee, Young Woo

Abstract

OBJECTIVE
AND METHODS: 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).
RESULTS
In media im-mediately 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.
CONCLUSIONS
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.