Smoking represents one of the most important preventable risk factors for the development of atherosclerosis. The present review aims at providing a comprehensive summary of published data from clinical and animal studies, as well as results of basic research on the proatherogenic effect of smoking. Extensive search and review of literature revealed a vast amount of data on the influence of cigarette smoke and its constituents on early atherogenesis, particularly on endothelial cells. Vascular dysfunction induced by smoking is initiated by reduced nitric oxide (NO) bioavailability and further by the increased expression of adhesion molecules and subsequent endothelial dysfunction. Smoking-induced increased adherence of platelets and macrophages provokes the development of a procoagulant and inflammatory environment. After transendothelial migration and activation, macrophages take up oxidized lipoproteins arising from oxidative modifications and transdifferentiate into foam cells. In addition to direct physical damage to endothelial cells, smoking induces tissue remodeling, and prothrombotic processes together with activation of systemic inflammatory signals, all of which contribute to atherogenic vessel wall changes. There are still great gaps in our knowledge about the effects of smoking on cardiovascular disease. However, we know that smoking cessation is the most effective measure for reversing damage that has already occurred and preventing fatal cardiovascular outcomes.

Objectives— Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of atherosclerosis. Methods and Results— In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters (ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.6[1.1.–2.3], P =0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm ² , P <0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies. Conclusion— Our research suggests Cd has promoting effects on early human and murine atherosclerosis, which were partly offset by high Zn concentrations.

Background: Cadmium is a potential new risk factor for early atherosclerosis and cardiovascular diseases in humans, yet pathogenetic mechanisms are still a matter of debate. Methods and Results: In-depth histological analysis of 18 sections taken from 6 cadmium-fed ApoE-/- mice and 12 sections from 5 litter-mates not exposed to cadmium by light and scanning electron microscopy was performed. Cadmium-fed mice showed a marked increase in lesion load (plaque area) and severity as classified according to the American Heart Association vascular lesion grading. All inflammatory markers studied (CD68, CD3, CD25, vascular cell adhesion molecule 1 (VCAM-1), and heat shock protein 60 (Hsp60)) yielded a higher expression in cadmium-fed mice. Statistical difference was achieved for VCAM-1 and Hsp60 (P=0.03 and P=0.02). The shoulder region of atherosclerotic plaques in cadmium-fed mice showed a prominent retraction of endothelial cells on electron microscopy. Conclusions: Our data indicate that cadmium exposure amplifies the development of vessel pathology in atherosclerosis susceptible ApoE-/- mice and suggests upregulation of VCAM-1 and Hsp60 and endothelial leakage as potential pathomechanisms. (Circ J 2011; 75: 2491-2495)

The present study was conducted to provide toxicological data on e-cigarette vapours of different e-cigarette brands and liquids from systems viewed as leaders in the e-cigarette market and to compare e-cigarette vapour toxicity to the toxicity of conventional strong high-nicotine cigarette smoke. Using an adapted version of a previously constructed cigarette smoke constituent sampling device, we collected the hydrophilic fraction of e-cigarette vapour and exposed human umbilical vein endothelial cells (HUVECs) to the mixture of compounds present in the vapour of 4 different single-use e-cigarettes, 6 different liquid vapours produced by the same refillable e-cigarette, and one e-cigarette with an exchangeable liquid cartridge. After incubation of cells with various concentrations and for various periods of time we analysed cell death induction, proliferation rates, the occurrence of intra-cellular reactive oxygen species, cell morphology, and we also measured e-cigarette heating coil temperatures. Overall, conventional cigarette smoke extract showed the most severe impact on endothelial cells. However, some e-cigarette vapour extracts showed high cytotoxicity, inhibition of cell proliferation, and alterations in cell morphology, which were comparable to conventional high-nicotine cigarettes. The vapours generated from different liquids using the same e-cigarette show substantial differences, pointing to the liquids as an important source for toxicity. E-cigarette vapour-mediated induction of oxidative stress was significant in one out of the 11 analysed vapours. There is a high variability in the acute cytotoxicity of e-cigarette vapours depending on the liquid and on the e-cigarettes used. Some products showed toxic effects close to a conventional high-nicotine cigarette. Liquid nicotine, menthol content, and the formation of acute intracellular reactive oxygen species do not seem to be the central elements in e-cigarette vapour toxicity.