Research Involves Nicotine In The Pathogenesis Of Atherosclerosis
It is a well-known fact that cigarette smoke is a risk factor for cardiovascular disease, along with obesity, high cholesterol levels, diabetes mellitus and others. Recently, a study conducted at Brown University in Providence, RI, uncovers how nicotine contributes to cardiovascular disease.
According to the study, nicotine determines the endothelium, cells lining blood vessels, to remodel. Blood vessels consist of three layers: adventitia, media, containing smooth muscle cells, and intima, consisting of endothelial cells. Nicotine promotes the invasion of vascular smooth muscle cells (VSMCs) from the media to the intima. In addition, nicotine causes invading cells to remodel. More specifically, the actin cytoskeleton forms podosomes, which regulate metalloproteinase (MMP) release for the extracellular matrix (ECM) degradation. Consequently, this fact leads to vessel degradation and, eventually, to atherosclerosis. The results of this study will be presented at the 56th Annual Meeting of the Biophysical Society (BPS), held in February. 25-29 in San Diego, California.
The fact that nicotine has the same effect as cigarette smoke on cardiovascular disease has to be confirmed by other studies. If the results are similar, than treatment with nicotine (patches, gum) used by those who want to quit smoking is not beneficial in order to reduce the risk of cardiovascular disease. Atherosclerosis is a process triggered as a result of an endothelial injury such as mechanical injury brought about by hypertension, hyperglycemia, high levels of low-density (LDL) lipoproteins or tobacco smoke. It is, in fact, an inflammatory process in the vessel wall in response to retention of low-density lipoproteins. Once inside the vessel wall, the low-density lipoproteins are oxidized thus leading to a cascade of immune responses which can lead to the formation of an atheroma . Now, nicotine itself appears to play an important role in atherosclerosis.
The discovery of a possible link between nicotine and podosomi in plaque formation could mean future therapeutic targets able to halt the process: targeting cell structures modified by nicotine, structures which promote blood vessel smooth muscle lining invasion. Intervention at this level could prevent or even stop the process of atherosclerosis.
An atheroma remains asymptomatic until it ulcerates, thus leading to immediate blood clotting. Progressively the clot enlarges and obstructs the blood vessel. Consequently, the downstream tissue is deprived of oxygen. If the blocked blood vessel is represented by a coronary artery the event leads to a myocardial infarction.
The lead researcher Chi-Ming Hai, professor of medical science in the Department of Molecular Pharmacology, Physiology, and Biotechnology at Brown University, notes that those who want to quit smoking using nicotine replacement therapy may need to reconsider their treatment option.