Atherosclerosis is a disorder of large and medium-sized muscular arteries and it is distinguished by inflammation, endothelial dysfunction and disposition of lipids, cholesterol, calcium and cellular debris inside the intima of the vessel wall. This loudening was results in plaque formation, vascular remodeling, irregularity of blood flow, acute and chronic luminal impediment, and diminished oxygen deliver to target organs .Arteriosclerosis is the major cause of death in the worldwide. About 16 million persons in the United States alone have atherosclerotic heart disorder and 5.8 million have stroke in 2005. Cardiovascular disease, chiefly atherosclerosis, caused almost 870,000 deaths in 2005—almost double as cancer caused and 9 times as injuries caused.
The risk factors for atherosclerosis are varied and they are corresponding in the presence of inflammatory state that is liable for atherosclerotic complication. There are many risk factors includes :
1. Non-modifiable risk factors like gender , age and genetic.
2. Modifiable risk factors such as hypertension ,dys-lipidaemia, hyperuriceamia, diabetes, drugs, infection, smoking , obesity and systemic autoimmune disease.
Atherosclerosis is an inflammatory disorder of the blood vessel wall, described in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages, dedifferentiation and movement of vascular smooth muscle cells to form the vastness of the atherosclerotic plaque. Atherosclerosis is not currently considered as a disorder due to abnormality in lipid metabolism. It has been extensively established that inflammation plays an essential role in atherosclerosis and causing all stages of this disease from beginning through progression and, ultimately, the thrombotic obstacles of atherosclerosis.
Oxidative stress has been identified through atherosclerosis, beginning at the early stage while endothelial dysfunction is barely apparent. As the process of atherosclerosis proceeds, large amounts of ROS liberated from inflammatory cells, as well as other ingredients of the atherosclerotic plaque, which further assist atherogenesis. In general, four essential mechanisms that contribute to atherogenesis occur due to improved in production of ROS may affect include: oxidation of LDL, vascular SMCs growth, endothelial cell dysfunction and monocytes migration.
Treatment of Atherosclerosis
1. Life style change
2. Medical Treatment:
A. Lipids modifying drugs:
1. HMG-CoA reductase inhibitors ( Pravastatin, Rosuvastatin, Lovastatin ,Fluvastatin, Atorvastatin ):
2. Fibric acid derivatives (Fenofibrate, Gemfibrozil ):
3. Bile acid sequestrants(Cholestyramine,Colestipol):
4. Cholesterol absorption inhibitors: Ezetimibe
5. Cholesteryl ester transfer protein inhibition (CETPi) Anacetrapib, dalcetrapib and torcetrapib
6. Phospholipase A2 inhibitors. darapladib and varespladib
There is association between improved intakes of antioxidant vitamins, including vitamins C, E, and beta-carotene, and decreased mortality from coronary artery disease. Antioxidants are thought to decrease the ox-LDL, reduce lipid accumulation in the arterial wall and enhance endothelial function.
4. New anti-inflammatory therapeutic approaches
The therapeutic potential of some anti-inflammatory agents have been estimated for possible anti atherosclerotic activity. Inflammation contributes to the creation and progression of atherosclerosis. Some agents with anti-inflammatory properties emerge to have beneficial actions on atherosclerosis or subsequent risk for cardiovascular events .
Nonsteroidal anti-inflammatory drugs (NSAID): celecoxib is selective inhibition of the COX-2 enzyme, prevents the improvement of atherosclerotic lesions in the proximal aortas from Apo E-/- mice through drop in expression of ICAM and VCAM (Jacob S. et al., 2000).
Pioglitazone ( peroxisome proliferator activator receptor PPAR-alpha and gamma) have established anti-inflammatory properties. It has been shown to decrease pro-inflammatory mediators like NF-KB, to reduce the expression of VCAM-1 and ICAM-1 in activated endothelial cells and significantly reduce macrophages and monocytes to atherosclerotic plaques (Libby P. and Plutzky J.,2007).
Tumor necrosis factor-[alpha] blocking agent (Etanercept) anti-TNF therapy can enhance other risk factors for accelerated atherosclerosis, including promoting a reduce in insulin resistance, CRP, IL-6, and an improve in HDL-C.(Haydar et al 2009).
A current study suggested that the risk for developing cardiovascular events in rheumatoid arthritis is less in patients treated with TNF antagonasts (Jacobsson LT. et al., 2005) .