Development of anti-atherosclerosis therapy based on the inflammatory and proliferative aspects of the disease

Atherosclerotic cardiovascular diseases are a worldwide major public health concern. Atherosclerosis is driven by a chronic inflammatory process which is present since the early stages of the disease, as a response to endothelium aggression by a variety of offending agents, to subsequent formation of foam cells, atheromatous plaque development and the clinical complications of the disease, due to plaque rupture and thromboembolic acute episodes. However, drug therapies directed to inflammation are lacking in the clinical practice, despite an increasing effort of research and identification of several potential molecular targets. Effective medical treatments available for primary and secondary prevention are restricted to cholesterol lowering statins and anti-platelet drugs such as aspirin. Here, steps of atherogenesis, cells involved in the process, secreted pro- and anti-inflammatory factors, the concept of unstable and stable atheroma plaques, the intertwining among inflammation, lipid arterial deposit, thrombus formation, therapeutically targetable mechanisms, monoclonal antibodies, enzymatic inhibitors, phytotherapeutic compounds and anti-proliferative agents used in cancer chemotherapy, drugs tested in experimental animals and at the clinical stage are shortly reviewed. Because statins and anti-platelet drugs use do not prevent more than 30-40% of the major cardiovascular events, the development of novel therapeutic tools is desirable. Nonetheless, atherosclerosis is a chronic process presumably demanding long-standing treatments, so that the safety, opportunity, cost-effectiveness and development of drug resistance are major issues that challenge the introduction of novel, inflammation-oriented therapies.