Innovative pharmaceutical interventions in experimental atherosclerosis : focusing on the contribution of non-HDL-C versus HDL-C

Abstract

Cardiovascular disease (CVD) is the leading cause of death worldwide despite the successful development of several pharmaceutical interventions of which statin therapy is the dominating lipid-lowering treatment option. Atherosclerosis, a chronic inflammatory disease of multifactorial origin, is a dominant contributor to the development of CVD. The research described in this thesis provides evidence for anti-atherogenic effects of several innovative pharmaceutical interventions that are currently being investigated in clinical trials, targeting hypertension and hypercholesterolemia, more specifically high low-density lipoprotein-cholesterol (LDL-C) and low high-density lipoprotein-cholesterol (HDL-C), as risk factors for CVD. Our results further support additional benefit of these treatment strategies in combination with statin treatment which is currently the __gold standard__ therapy for the treatment of CVD. Most of these lipid-modifying treatment strategies affect both LDL-C and HDL-C and we demonstrate that the beneficial effects of these treatment strategies predominantly derive from their non-HDL-C/LDL-C-lowering abilities. Nonetheless, results from preclinical studies and clinical trials support the notion that treatment strategies aimed at improving HDL function and raising apolipoprotein A-I may also inhibit the development of atherosclerosis and reduce the prevalence of CVD.