Student ID 375511

Subject code 514751

The role of tobacco smoking in atherosclerosis progression

According to the data obtained from several epidemiological studies carried out by multiple countries, tobacco smoking (TS) has been estimated as the largest risk factor for cardiovascular diseases (Fagard, 2009). TS has been proposed to lead to vascular dysfunction, accelerate the progression of atherosclerosis, and promote acute arterial thrombosis and myocardial infarction (Ambrose & Barua, 2004). In this essay, I will briefly introduce the biological mechanism underlying the progression of atherosclerosis and discuss the impacts of TS on each stage of this process.

Atherosclerosis is characterized by the histopathological change of the arterial wall, including the deposits of lipid crystal (mainly cholesterol) and the formation of the yellowish fibrous cap. Atherosclerosis starts with the presence of oxidized-LDL (Low Density Lipoprotein) getting trapped inside the endothelial wall of the artery, which subsequently triggers inflammatory response, thus recruiting macrophages to the affected site. Macrophages take up the oxidized-LDL through their scavenger receptors and become foam cells, which then deposit their cholesterol content at the affected site. This process would continue for years until the atherosclerotic plague ruptures and results in severe clinical outcomes (Libby & Braunwald, 2008). Although atherosclerosis is a chronic and progressive disease, its progression can be evidently accelerated by TS (Winkelmann, 2009).

TS exerts negative impacts on every stage of the progression of atherosclerosis. First

Student ID 375511

Subject code 514751

of all, in both animal and human models, smoking has been shown to impair the vasodilatory function of the artery (Ambrose & Barua, 2004), therefore amplifies the opportunity for circulating LDL to get trapped inside the arterial wall and get oxidized. Secondly, smoking increases the free radical and oxidative stress level in smoking individuals (Winkelmann, 2009). Therefore it has a direct role in increasing the level of oxidized-LDL thus triggers the subsequent inflammatory response. In addition, it also contributes to the progression of atherosclerosis by oxidizing nitrogen monoxide (NO). In functional arteries, NO not only acts as an antioxidant and prevents LDL from being oxidized, but also a potent vessel dilator. Thirdly, smoking also impairs the formation of NO by the endothelial cells lining the arterial wall. NO is synthesized from L-arginine by enzymes called NOS. According to the extensive study of the disturbances of the NOS pathway, the mechanisms could involve the reduction in NO half-life and reduced NOS activity (Winkelmann, 2009).

Furthermore, TS induced peripheral leukocytosis was observed in several studies (a 20% to 25% increase), indicating its role in inducing inflammation, which serves as an initial stage for the formation of atherosclerotic plaque (Ambrose & Barua, 2004). Finally, TS has been proposed to directly change the lipid profiles of smoking individuals, who are shown to have a higher proportion of LDL while a lower proportion of HDL in comparison to non-smokers (Ambrose & Barua, 2004). HDL is often referred to the good cholesterol as they recycle the cholesterol back to the liver for degradation or re-utilization.

Student ID 375511

Subject code 514751

It is clear that TS accelerate the progression of atherosclerosis by impairing the vasodilatory function of the artery, impairing the formation of and oxidizing nitrogen monoxide, as well as inducing inflammation. However, since the underlying mechanism has not been fully elucidated, only some of the well established mechanisms are discussed in this essay. Clearly more research is necessary in order to explore the more detailed mechanism that underlies the action of TS on the progression of atherosclerosis.

Student ID 375511

Subject code 514751

References Ambrose, J. A., & Barua, R. S. (2004). The pathophysiology of cigarette smoking and cardiovascular disease: An update. Journal of the American College of Cardiology, 43(10), 1731-1737. doi: DOI: 10.1016/j.jacc.2003.12.047 Fagard, R. H. (2009). Smoking amplifies cardiovascular risk in patients with hypertension and diabetes.(SMOKING). Diabetes Care, 32(11), S429(423). Libby, P., & Braunwald, E. (2008). Braunwald's heart disease : a textbook of cardiovascular medicine (8th ed.). Philadelphia: Saunders/Elsevier. Winkelmann, B. (2009). Smoking and atherosclerotic cardiovascular disease: Part I: Atherosclerotic disease process. Biomarkers in medicine, 3(4), 18.