Oxidized lipids and programmed cell death in atherosclerosis
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: A heart attack or myocardial infarction is America's number one killer. It usually happens because of a blockage in a coronary artery, which prevents blood from being delivered to heart tissue. Usually arterial blockage is caused by atherosclerosis, a form of artery disease that is characterized by a buildup of fatty deposits and chronic inflammation along inner artery walls. These deposits gradually develop into plaques that narrow blood vessels and eventually lead to rupture of the plaque, clotting of the blood (thrombosis) and interruption of blood flow, which lead to clinical event (myocardial infarction or stroke). Cigarette smoking and high blood cholesterol levels are major risk factors for the development of atherosclerosis. However, the mechanisms involved in the development of atherosclerosis are complex and remain unknown. Usually, someone who has a high blood cholesterol level has a high level of low-density lipoprotein (LDL) in blood. LDL is composed of lipid (fat, mainly cholesterol) and protein, and is considered the “bad”" form of cholesterol because it tends to collect in artery walls and develop into atherosclerotic plaque. When LDL is oxidized in the arterial wall, it becomes “oxidized LDL". Oxidized LDL is preferentially accumulated by macrophages, the scavenger cells found in early atherosclerotic lesions, and contributes to the cholesterol accumulation that is typical of atherosclerosis. Oxidized LDL and its related compounds also have properties that induce inflammation in the arterial walls which further develop the atherosclerotic plaque. 
 
 
 
 
 
 Apoptosis is an active form of cell death in which cells neatly commit “programmed suicide” to be taken up and cleared by neighboring cells in normal tissues. Apoptosis plays an important role in maintaining proper turnover of cells in the body by removing damaged or aged cells. Normally the clearance of apoptotic cells occurs swiftly and efficiently so that it is hard to detect apoptotic cells in normal tissues. If apoptotic cells are not cleared up promptly noxious contents of the cell will leak out and induce direct tissue injury and inflammation. In atherosclerotic lesions, a lot of apoptotic cells are present in addition to the fatty deposits. These apoptotic cells may be one of the causative factors that disrupts the atherosclerotic plaque, which in turn causes the acute blood clotting and vessel blockage leading to myocardial infarction. 
 
 
 
 
 
 
 
 In preliminary studies I found that apoptotic cells present oxidatively modified lipid and/or lipid-protein molecules on their surfaces, and that these oxidized molecules could serve as “markers” for the clearance of apoptotic cells. I hypothesize that apoptotic cells may play a similar role to oxidized LDL in the development of advanced atherosclerotic lesion. The proposed studies will seek to define the mechanism involved in the clearance of apoptotic cells and the impact of their defective clearance on atherosclerosis. These findings will increase our knowledge of the etiology of atherosclerosis, which in turn could lead to prevention and improved therapies.