Introduction

Crucial advances in our understanding of atherogenesis have been achieved during the past two decades. The historical hypothesis of pathogenesis (‘lipid accumulation’) has evolved to integrate several pathogenic mechanisms contributing to the initiation and evolution of atherogenesis. Vascular inflammation and apoptosis may play pivotal roles in its progression and onset. Endothelial dysfunction is considered to be one of the earliest events in atherogenesis. This chapter will discuss emerging concepts in the pathogenesis of, and therapeutic approaches to, atherosclerosis. Some novel risk factors, including impaired fasting glucose, triglycerides and triglyceride-rich lipoprotein remnants, lipoprotein (a), homocysteine, and high-sensitivity C-reactive protein, might contribute to an increased risk of atherosclerosis (Fruchart et al. 2004). Moreover, hypercholesterolaemia and hypertension have synergistic deleterious effects on coronary endothelial function (Rodriguez-Porcel et al. 2003). The pathogenesis of atherosclerosis has been related also to infiltration of immune cells, which are involved in systemic and local, innate as well as adaptive, immune responses (Zhou and Hansson 2004). As some inflammatory and autoimmune diseases could be treated by immunologically based therapy, it is of particular interest to consider whether such principles could also be applied to prevent or treat atherosclerosis.

Atherosclerosis is ultimately responsible for myocardial infarction, peripheral arterial disease and ischaemic stroke, and is characterised by a long lag-time between onset and clinical manifestation. The prodromal stages of human atherosclerotic lesions are already formed during fetal development (Napoli et al. 1997a, 1999a, Palinski and Napoli 2002a). Intimal thickening is also observed in fetal coronary arteries (Ikari et al. 1999).