Therapeutic approaches to drug targets in atherosclerosis

Abstract

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis.

Keywords: Atherosclerosis; Drug targets; Endoglin; Heat shock protein; Hyperlipidemia.

Figure 1

Shows the atherosclerosis-plaque develops in the coronary arteries.

Figure 2

Shows endothelial injury progression for atherosclerosis initiation model. Several risk factors, such as hypertension, elevated oxidized low density lipoprotein level, hyperglycemia, cigarette smoking, and homocysteine promote atherogenesis through upregulation of genes and activation of macrophages and T-lymphocytes and increase lipid deposition. The top of the figure represents the intraluminal space, and the bottom represents the subendothelial matrix, and SMC.

Figure 3

Shows the role of soluble endoglin in atherosclerosis: cardiovascular diseases like atherosclerosis, hypertension, diabetes mellitus and preeclampsia, increase levels of soluble endoglin in blood in humans that leads to increased interactions between endoglin and TGFb1 in blood followed by reduced TGF-b signaling in vessels, thus promoting atherogenesis. Statins, reduction of cholesterol levels and application of extracorporeal procedures decrease soluble endoglin levels in blood, which may result in an increased TGFb1 signaling in the vessel wall and possibly affect atherogenesis (Petr et al., 2012).