The Impact of Cigarette Smoking on HDL Composition and Function
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It has been known for decades that cigarette smoking is associated with atherosclerosis; however, the specific mechanisms for this association remain unclear. High density lipoprotein (HDL) is known to play a key atheroprotective function by removing excess cellular cholesterol, thereby reversing atherosclerotic lesion formation. Here, we investigate whether smoking causes oxidation of HDL proteins, leading to loss of function. We utilized three separate study populations to interrogate HDL function, protein modification, particle size, and protein cargo--each of which provides distinct information about HDL and its potential roles in biological processes. We observed altered HDL function, particle subpopulations, and protein cargo in smokers. Notably, HDL levels of alpha-1 antitrypsin, an acute phase protein, were positively associated with smoking status. These observations have implications for a role of smoking in generating modified forms of HDL that promote atherosclerosis.