Cigarette-smoke-induced atherogenic lipid profiles in plasma and vascular tissue of apolipoprotein E-deficient mice are attenuated by smoking cessation

Abstract

Tobacco smoke exerts perturbations on lipid metabolism and arterial cell function that accelerate atherosclerosis. Lipidomics has emerged as a key technology in helping to elucidate the lipid-related mechanisms of atherosclerosis. In this study, we investigated the effects of smoking cessation on plaque development and aortic arch content of various lipid molecular classes and species. Apolipoprotein E-deficient mice were exposed to fresh air (sham) or to mainstream cigarette smoke (CS) for 6 months, or to CS for 3 months followed by sham for 3 months (cessation group). Lipids from plasma and aortic arches, plasma lipoprotein profiles and plaque morphometry measurements were analyzed. We already showed that CS exposure accelerated plaque size and total cholesterol content of the aortic arch at 3 and 6 months. Marked increases were seen in the relative enrichment of cholesteryl esters, phospholipids, sphingomyelins, and glycosphingolipids. Smoking cessation slowed plaque progression and resulted in lower levels of many lipid species in plasma and aortic arch. While CS exposure promoted rapid lipid accumulation in mouse aorta, smoking cessation translated into a slow removal of lipids from the vessel wall. Despite the smoking cessation-dependent metabolic changes leading to increased animal body weight, accumulation of proatherogenic lipids in the vessel was halted after exposure cessation, indicating that the clinical benefits of smoking cessation translate directly to the vessel wall and its lipid makeup.

A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

“…S1P receptor is expressed by ECs and it binds its ligand S1P, a bioactive lipid with numerous functions in the immune and cardiovascular systems. Using a lipidomics approach, we have previously shown that CS exposure increases, whereas cessation decreases, the levels of S1P in plasma of ApoE -/- mice [5,22]. Furthermore, CD36 is a glycoprotein expressed in various vascular and circulatory cell types including monocytes, macrophages, platelets, ECs and adipocytes.…”

“…We used the V-IPN network to assess the degree of biological mechanistic coverage from four different sets of transcriptomics profiling data derived from multiple atherosclerotic-relevant contexts including human endothelial cells (ECs) in culture, coronary arteries from coronary artery disease (CAD) patients and aortas from ApoE -/- mice. The systemic inflammatory status of ApoE -/- mice, a well-established model of atherosclerosis [21], makes this strain an ideal model in which to study comorbidities associated to cigarette smoking [22]. Our results indicate that the V-IPN captures the key biological mechanisms that underlie the progression of vascular disease in various cellular and tissue contexts and allows for a comprehensive interrogation of transcriptomics datasets related to atherogenesis and cross-species translatability.…”

Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis

“…In mouse models exposure to mainstream cigarette smoke led to perturbations of lipid metabolism, arterial endothelial cell function and the development of atherosclerotic lesions (Boue et al, 2012). Cessation of smoke exposure led to decelerated plaque progression and decreased accumulation of pro-atherogenic lipids (Lietz et al, 2013). …”

How to address smoking cessation in HIV patients

“…There is evidence among nondiabetic individuals that potential weight gain after stopping smoking has no impact on the expected reduction of CVDR . In apolipoprotein E‐deficient mice, cessation of exposure to cigarette smoke led to lower levels of proatherogenic lipid species in plasma and vessel walls . Additionally, plasma levels of endothelial progenitor cells, which are usually low in smokers, tend to recover their normal range after smoking cessation .…”