Oxidized LDL is a “life-threatening, killer molecule.” This is because oxidized LDL plays a major role in the pathophysiology of coronary artery disease, which is the leading cause of death in the United States and the Western world. Oxidized LDL is a plaque-specific protein; which is found in atherosclerotic plaques. Oxidized LDL is not found in healthy arteries.
Oxidized LDL molecules are directly involved in the early stages of atherosclerosis in the artery wall, from the transformation of monocyte/macrophages into lipid-laden foam cells to the development of the first visible lesion of atherosclerosis, the fatty streak.
There is experimental evidence demonstrating that oxidized LDL may actually be the inflammation-producing agent in the coronary artery lesion. As an inflammation-producing agent, oxidized LDL appears to stimulate the biosynthesis and release of cytokines in the artery wall; these cytokines, in turn, go to the liver where
they stimulate the synthesis of systemic markers of inflammation (acute phase proteins), such as C-reactive protein (CRP) and fibrinogen.
The release of cytokines attracts more white blood cells and perpetuates the whole cycle, causing persistent injury and inflammation to the arteries. The injured inner vessel walls fail to produce enough nitric oxide, which is critical for maintaining the elasticity of blood vessels. Eventually, the inelastic and plaque-laden arteries narrow and restrict the flow of oxygen-rich blood to the heart.
In the later stages of coronary artery disease, when the atherosclerotic plaque becomes unstable and begins to rupture or has already ruptured, as in acute coronary syndromes (unstable angina and acute myocardial infarction), oxidized LDL molecules (particularly malondialdehyde-modified LDL) are released from the plaque into the circulation. It has been hypothesized that oxidized LDL, by itself, may be responsible for producing plaque instability.
Elevated circulating levels of oxidized LDL are found in patients with chronic and acute coronary artery disease. There is no other coronary artery disease biomarker currently available that has the very high diagnostic sensitivity and specificity of oxidized LDL. Elevated oxidized LDL levels in the plasma/serum of coronary artery disease patients seem to reflect increased amounts of oxidized LDL present in the atherosclerotic plaques. Elevated circulating levels of oxidized LDL indicate accelerated atherosclerosis (increased atheroclerotic disease activity).
OXIDIZED LDL AND HDL: ANTAGONISTS IN ATHROTHROMBOSIS
Oxidized LDL and HDL levels are inversely related to the risk of Coronary Artery Disease. Oxidized LDL induces atherosclerosis by stimulating monocyte infiltration used with both OxLDL and HDL, and smooth muscle cell migration and proliferation.
HDL prevents atherosclerosis by reverting the stimulatory effect of oxidized LDL on monocyte infiltration used with both OxLDL and HDL, and attributing to reverse cholesterol transport.