The effects of second-hand smoke on biological processes important in atherogenesis.
BACKGROUND
Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis.


METHODS
To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB100 was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation.


RESULTS
"Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein-1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke) to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice.


CONCLUSIONS
Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that leads to lipid accumulation in the liver and in the blood vessels of the heart and aorta. The former potentially can lead to non-alcoholic fatty liver disease and the latter to heart attacks.
Yuan
Hongwei
H
Graduate Program in Cell, Molecular and Developmental Biology, University of California, Riverside, Riverside, California, USA. hyuan001@student.ucr.edu <hyuan001@student.ucr.edu>
Wong
Lina S
LS
Bhattacharya
Monideepa
M
Ma
Chongze
C
Zafarani
Mohammed
M
Yao
Min
M
Schneider
Matthias
M
Pitas
Robert E
RE
Martins-Green
Manuela
M
D052242:Adiponectin / Q000097:blood; D000818:Animals; D001011:Aorta / Q000378:metabolism; D053299:Apolipoprotein B-100 / Q000235:genetics; D001158:Arteries / Q000473:pathology; D050197:Atherosclerosis / Q000209:etiology*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000209:etiology; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D053299:Apolipoprotein B-100; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D008055:Lipids; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha