Smoking and Atherosclerotic Cardiovascular Disease: Part I: Atherosclerotic Disease Process

Abstract

The normal endothelium inhibits platelet and leukocyte adhesion to the vascular surface maintaining a balance of profibrinolytic and prothrombotic activity. Endothelial function is assessed largely as endothelium-dependent vasomotion, partly based on the assumption that impaired endothelium-dependent vasodilation reflects the alteration of important endothelial functions. Atherosclerotic risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking, are associated with endothelial dysfunction. In the diseased endothelium, the balance between pro- and antithrombotic, pro- and anti-inflammatory, pro- and antiadhesive or pro- and antioxidant effects shifts towards a proinflammatory, prothrombotic, pro-oxidative and proadhesive phenotype of the endothelium. A common mechanism underlying endothelial dysfunction is related to the increased vascular production of reactive oxygen species. Recent studies suggest that inflammation per se, and C-reactive protein in particular, may contribute directly to endothelial dysfunction. The loss of endothelial integrity is a hallmark of atherosclerosis and the causal possible link between each individual risk factor, the development of atherosclerosis and the subsequent clinical events, such as myocardial infarction or stroke.

KEYWORDS::

• atherosclerosis
• biomarker
• cardiovascular disease
• cigarette smoking

Acknowledgements

The authors gratefully acknowledge the support of L Conroy in the editing process and of the library staff of Philip Morris USA and of Philip Morris Research Laboratories GmbH, Germany, for managing all activities related to searching for and organizing the references.

Financial & competing interests disclosure

This work was supported in part by Philip Morris International, Inc. This work was also supported in part by Philip Morris USA, Inc., prior to the spin-off of Philip Morris International, Inc., by Altria Group, Inc. on 28 March, 2008. The opinions and conclusions of the researchers are their own and do not necessarily reflect Philip Morris International, Inc.‘s position. Klaus von Holt is a former employee of Philip Morris International, Inc., now serving as a consultant. Martin Unverdorben is also a former employee of Philip Morris USA, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

* Biomarkers with multiple effects are listed according to their major mode of action.

‡ Despite also being referred to as endothelial cell superoxide isomaltose, it is the vascular smooth muscle cell and not the endothelium that is the major source for the secretion of this potent antioxidant enzyme [141].

Modified from [147,148].

Additional information

Funding

This work was supported in part by Philip Morris International, Inc. This work was also supported in part by Philip Morris USA, Inc., prior to the spin-off of Philip Morris International, Inc., by Altria Group, Inc. on 28 March, 2008. The opinions and conclusions of the researchers are their own and do not necessarily reflect Philip Morris International, Inc.‘s position. Klaus von Holt is a former employee of Philip Morris International, Inc., now serving as a consultant. Martin Unverdorben is also a former employee of Philip Morris USA, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.