Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

Abstract

Abstract-Acute rupture or erosion of a coronary atheromatous plaque and subsequent coronary artery thrombosis cause the majority of sudden cardiac deaths and myocardial infarctions. Cigarette smoking is a major risk factor for acute coronary thrombosis. Indeed, a majority of sudden cardiac deaths attributable to acute thrombosis are in cigarette smokers. Both active and passive cigarette smoke exposure seem to increase the risk of coronary thrombosis and myocardial infarctions. Cigarette smoke exposure seems to alter the hemostatic process via multiple mechanisms, which include alteration of the function of endothelial cells, platelets, fibrinogen, and coagulation factors. This creates an imbalance of antithrombotic/ prothrombotic factors and profibrinolytic/antifibrinolytic factors that support the initiation and propagation of thrombosis.

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

“…Moreover, our data revealed that the e‐cigarette–exposed platelets are less sensitive to inhibition by PGI 2 , in comparison to those from clean air; which may have also contributed to the thrombosis phenotype in these mice. Importantly, these results are also “similar” to those observed with traditional tobacco smoke, which heightens platelet activation (eg, aggregation)17, 94 and renders platelets less sensitive to PGI 2. 95 On the other hand, we observed no difference in the activation state of leukocytes between e‐cigarettes and clean air.…”

“…After “validating” our model, we first sought to investigate the impact of e‐cigarettes on thrombogenesis, as it is the major cause of tobacco‐induced CVD,38 including thrombosis‐based diseases 17, 77, 78, 79, 80, 81, 82, 83. Our findings revealed, for the first time, a drastic reduction in the time for carotid artery occlusion, indicating a prothrombotic phenotype, even after only a week of whole‐body exposure to e‐cigarettes.…”

“…However, this study neither mimicked real‐life conditions (eg, employed e‐cigarette extracts) nor used an in vivo whole‐body exposure model to investigate the effects of e‐cigarettes on platelets. It is noteworthy that thrombosis is the main mechanism of cardiovascular mortality in smokers17; smoking causes a prothrombotic state through altering fibrinolytic and thrombotic factors17, 18; smokers’ isolated platelets exhibited increased aggregation19, 20; and exposure to cigarette smoke alters the dynamics of clot formation, making them more resistant to thrombolysis as compared with clots of nonsmokers 21, 22, 23. However, whether e‐cigarettes exert similar effects is yet to be determined and warrants investigation.…”

Stabilization of high-risk plaques

“…Smoking elevates the expression of soluble adhesion molecules, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) in ECs. Exposure to cigarette smoke increased intraplaque inflammation and neovascularization, which leads to intraplaque hemorrhage and consequent necrotic core formation (160). Nicotine affects serum thromboxanes A2/B2 and catecholamines, which enhance platelet activation (12).…”

Absence of Smoker’s Paradox in Middle Eastern Patients with Acute Coronary Syndrome

“…Cigarette smoking is a well-established modifiable risk factor for atherosclerotic coronary artery disease (CAD) [1][2][3]. It is known for its role in impairing endogenous fibrinolysis, enhancing platelet aggregation and thrombus formation, and promoting the development of a thin fibrous cap in atherosclerotic coronary plaques, thus predisposing the plaque to erosion and subsequent thrombosis leading to acute coronary syndrome (ACS) [4][5][6][7].…”