Local intravascular delivery of low-density-lipoprotein cholesterol corresponds with increased intimal thickening in a healthy porcine coronary model. A prelude to development of a model of atherosclerosis

Abstract

Introduction

Preclinical, vascular response studies are limited due to lack of underlying disease. The available cholesterol-diet-based and genetic atherosclerotic models are not satisfactory due to long breeding, unpredictable lesion formation, low plaque volume and degree of stenosis.

Aim

To evaluate the vascular response to local, intramural delivery of human, highly atherogenic lipids into healthy domestic swine (DS) coronary arteries.

Material and methods

A total of 24 coronary artery segments of 10 DS were enrolled. Following balloon injury (plain old balloon angioplasty – POBA), segments were assigned to local delivery of 2 ml of human LDL from apheresis (400 mg/dl, n = 9), 0.9% NaCl (control, n = 7) or to POBA alone. The solutions were infused with a modified, triple micro-needle catheter into the vessel wall. After 28 days, optical coherence tomography (OCT), virtual histology IVUS (VH-IVUS) and near-infra-red spectroscopy (NIRS) were performed. Following euthanasia, vessel segments were harvested for pathological evaluation.

Results

At 28 days the % area stenosis in OCT was highest in the LDL group (23.6 ±13 vs. 10.8 ±7 vs. 8.1 ±7%; p = 0.02). The presence of necrotic core (LDL: 55.5%, control: 37.5% and POBA: 42.8%; p = 0.77) and dense calcium (LDL: 33.3%, control: 28.5%, POBA: 37.5%; p = 0.94) in VH-IVUS were comparable between groups. The lipid core burden index in NIRS was negative in all cases. In pathology, the injury was comparable between groups (LDL: 1.6 ±0.4, control: 1.7 ±0.8, POBA: 1.7; p = 0.8) and specimens showed no signs of necrotic or lipid core. The tissue consisted of smooth muscle cells (SMC)/proteoglycan-rich lesions and inflammatory cells.

Conclusions

Local delivery of saturated human LDL into the coronary artery wall was feasible and resulted in a higher degree of stenosis caused by intimal thickening. A discrepancy between histopathological findings and virtual histology intravascular ultrasound (VH-IVUS) was also noted.