Plasma antioxidant enzymes as markers of smoke injury
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The proposed research examines the health related effects of cigarette smoking on heart disease. It is well known that smoking is a prime factor in contributing to heart disease but exactly how smoking contributes is not completely understood. It is now generally accepted that early events in heart disease, i.e., atherosclerosis, are initiated by oxidized low density lipoproteins (LDL) in the blood. Oxidative modification of LDL triggers a series of responses that include inflammation responses that subsequently result in the migration of certain white cells (monocytes) from the blood into the artery wall. There the monocytes are converted into macrophages which essentially sequester or take up the oxidized LDL. This leads to the formation of “foam” cells in the artery wall; accumulation of foam cells leads to fatty streak formation and continued insults result in atheromas which can be life threatening. Clearly, protection of LDL from oxidation is paramount to maintaining the integrity of these particles and reducing risk for atherosclerosis. However, cigarette smoke is known to contain oxidizing molecules and other components that can also stimulate oxidative bursts in the blood; both have the potential of oxidizing plasma LDL. The plasma also contains antioxidant enzymes that normally protect LDL from oxidant injury. Interestingly, some of these enzymes are actually associated with high density lipoprotein (HDL), which is known to be protective against heart disease. 
 
 
 
 
 
 
 
 The antioxidant enzymes of interest function by hydrolyzing (breaking down) the oxidized lipids which appear on LDL in the progression of oxidant injury. It is the oxidized lipids that initiate the cascade of events that lead to inflammation and foam cell formation. Our premise is that, if these enzymes are impaired as a consequence of cigarette smoking, LDL will be modified and will become atherogenic. To test this hypothesis, we plan to investigate the acute effects of cigarette smoking in a group of young smokers. The subjects will be asked to smoke 6 cigarettes over a 1 hour period and blood samples will be taken before and after that smoking period. The blood plasma will be assayed for antioxidant enzyme activity; in addition, we will directly quantify oxidized lipids on the LDL from smoking subjects and compare it with the nonsmoking state. A reduction in plasma antioxidant enzyme activity and an increase in LDL oxidized lipids will signal the likelihood that cigarette smoke has compromised these very important protective factors in the blood. These outcomes would predispose smokers to increased risk for cardiovascular disease. The results of these studies will provide new insights into mechanisms whereby smoking can contribute to heart disease. A demonstration of the deleterious effects of smoking on plasma antioxidant enzymes will enable physicians to better advise patients on the dangers of smoking to their health, particularly the cardiovascular system. This may serve as a deterrent to smoking. The information gleaned from these studies may also be useful for developing strategies for ameliorating the adverse health effects resulting from oxidation of LDL as a consequence of impaired antioxidant enzyme activity.