Title:Development of Anti-Atherosclerosis Therapy Based on the Inflammatory and Proliferative Aspects of the Disease
Volume: 21
Issue: 9
Author(s): Raul C. Maranhao and Antonio C. A. Leite
Affiliation:
Keywords:
Inflammation in atherosclerosis, cardiovascular disease treatment, anti-inflammatory drugs, atherosclerosis pathophysiology.
Abstract: 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.
