© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty
aCenter for Molecular and Vascular Biology, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
bCentre for Experimental Surgery and Anaesthesiology, Katholieke Universiteit Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
cKlinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, University of Münster, Münster, Germany
dDepartment of Pathology—CMU, Geneva, Switzerland
eAZ—Middelheim and Department of Pharmacology, University of Antwerp, Antwerp, Belgium
* Corresponding author. Tel.: +32-16-34-7149; fax: +32-16-34-7114 paul.holvoet{at}med.kuleuven.ac.be
Objective: To assess the effect of hypercholesterolemia on neointima formation and vascular remodelling after porcine coronary angioplasty. Methods: Left anterior descending coronary angioplasty was carried out in five control and 16 age-matched hypercholesterolemic miniature pigs. Vascular remodelling was measured by intravascular ultrasound. Neointima size and composition were assessed by quantitative image analysis. Coronary smooth muscle cells (SMC) from control and diet pigs were collected 1 h after angioplasty for in vitro study of the effect of hypercholesterolemic serum on SMC migration and of macrophage-induced matrix degradation on SMC adhesion. Results: Twenty-eight days after angioplasty, lumen increase was 0.08±1.7 mm2 in diet and 2.7±2.7 mm2 (P = 0.016) in control pigs. Lumen increase correlated with vascular remodelling (IELpost/IELpre; R2=0.59; P<0.001) and with the circumferential gain relative to the neointima (R2=0.32; P<0.01) but not with neointimal area that was similar in control and diet pigs. Circumferential gain correlated with VSMC deposition at the site of the injury (R2=0.28; P<0.01) that correlated with organized collagen (R2=0.34; P<0.01). The VSMC and collagen content of neointima in diet pigs was lower whereas the macrophage content was higher. Hypercholesterolemic serum and oxidised LDL reduced migration of VSMC from diet pigs. Macrophage-induced degradation of VSMC extracellular matrix reduced VSMC adhesion (P = 0.015). Conclusion: Hypercholesterolemia impairs vascular remodelling of balloon-treated coronary arteries. It decreases VSMC and collagen accumulation at the site of injury. Our in vitro data suggest that this decrease can be due to macrophage-induced matrix degradation and reduced VSMC adhesion and to impaired VSMC migration. Oxidised LDL mimics the inhibitory effect of hypercholesterolemic serum.
KEYWORDS Angioplasty; Atherosclerosis; Lipoproteins; Macrophages; Smooth muscle
1 These authors contributed equally to the studies.
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