The pro-atherogenic role of Intimal hyperplasia

Abstract

Atherosclerosis is a leading cause of mortality worldwide, and results from accumulation of plasma lipoproteins, mainly low-density lipopro-teins (LDL), in the sub-endothelial layer of the arterial wall. In this the-sis, I investigated how structural changes of the vessel wall can make the vessel more prone to developing atherosclerotic lesions. Project 1: Accelerated atherosclerosis occurs following vascular inter-ventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of the accelerated athero-genesis is not known. We found that intimal hyperplasia induced by vascular interventions makes the vessel wall highly susceptible to LDL retention and accelerated atherosclerosis by a mechanism that can be targeted by glycosaminoglycan (GAG)-binding antibodies. Project 2: Cadmium is an important risk factor for athero-sclerosis, but the underlying mechanism for how cadmium increases the risk of ather-osclerosis is unclear. We observed: (1) increased expression of perlecan and the GAG-chain modifying enzyme CHST3 in arteries following local exposure to cadmium; and (2) increased LDL-binding in proteo-glycans isolated from cells cocultured with cadmium. Finally, we showed that local cadmium exposure increased LDL retention in the arterial wall. Project 3: Immunofluorescence microscopy is a method used to study the spatial location of proteins in tissues and cells. Here we present an enhanced multi-fluorescence setup based on condensed filter sets that are more specific for each fluorochrome and allow for a more efficient use of the light spectrum.