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How does oxidized HDL affect reverse cholesterol transport?
Oxidized HDL (oxHDL) disrupts reverse cholesterol transport (RCT)—one of the key protective functions of high-density lipoprotein (HDL)—by interfering with its ability to remove cholesterol from peripheral tissues and deliver it to the liver for excretion. Here’s how:
Normal HDL Function in Reverse Cholesterol Transport
Cholesterol Efflux: HDL accepts excess cholesterol from macrophages in the walls of arteries via transporters (like ABCA1 and ABCG1).
Cholesterol Esterification: HDL uses LCAT, or lecithin-cholesterol acyltransferase, to esterify free cholesterol into cholesteryl esters.
Transport to Liver: Mature HDL delivers the cholesterol to the liver with the receptor SR-BI, or transfers the cholesterol to other lipoproteins for uptake by the liver.
❌ What Happens When HDL Is Oxidized
Impaired Cholesterol Efflux: oxHDL has an inefficient reception of cholesterol from the macrophages, thereby inhibiting the initial RCT step.
Dysfunctional ApoA-I: Oxidation alters apolipoprotein A-I, the main protein in HDL, impairing its interaction with cholesterol transporters.
Inhibited LCAT Activity: oxHDL may have decreased ability to activate LCAT, stalling cholesterol esterification.
Pro-inflammatory Profile: oxHDL can switch from being anti-inflammatory to pro-inflammatory, promoting atherosclerosis.
Decreased SR-BI Binding: oxHDL interacts poorly with hepatic receptors, lowering cholesterol delivery to the liver.
???? Summary
Instead of protecting against cardiovascular disease, oxidized HDL is dysfunctional, loses its cholesterol-clearing ability, and can even promote plaque buildup and inflammation.
Would you like to view a diagram of the difference between normal and oxidized HDL in RCT?
Conjugated dienes are pertinent to oxidized cholesterol because they are early indicators of lipid peroxidation, a detrimental oxidative process that alters the structure and function of cholesterol and other lipids.
Below is a discussion of their significance:
1. Early Markers of Oxidation
Conjugated dienes result from the oxidative stress (attack by reactive oxygen species, or ROS) of polyunsaturated fatty acids or cholesterol.
Oxidation reconfigures double bonds within the lipid or cholesterol molecules to create conjugated double bonds (i.e., alternating double and single bonds).
These structures absorb UV at ~234 nm, so their formation is often monitored spectrophotometrically.
2. Role in Atherogenesis
Oxidized cholesterol, specifically oxysterols, is involved in the development of atherosclerosis (hardening and narrowing of the arteries).
Pro-inflammatory, cytotoxic conjugated dienes in oxidized LDL (low-density lipoprotein) promote:
Endothelial dysfunction
Foam cell formation
Plaque instability
3. Indicator of Food and Biological Lipid Stability
In the food industry, conjugated diene levels are used for the determination of lipid rancidity and shelf life in products with cholesterol (e.g., meat or dairy).
Levels elevated in biological fluids (plasma) indicate increased oxidative stress or risk for cardiovascular disease.
4. Biochemical Implication
Conjugated dienes show that the process of lipid and cholesterol oxidation is beyond the beginning stages, in which chain reactions of lipid peroxidation involving the production of more harmful substances like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) is occurring.
Conclusion
Conjugated dienes are molecular fingerprints of cholesterol oxidation. They are utilized to identify and measure oxidative damage in cells, foods, and plasma and are necessary for researching and monitoring diseases like atherosclerosis, inflammation, and lipid stability.
Would you like a diagram of the formation of conjugated dienes through the oxidation of cholesterol?
Ironbound™ A Strategy For The Management Of Hemochromatosis By Shelly Manning if you are suffering from the problems caused by the health condition of HCT due to excess amount of iron in your body then instead of using harmful chemical-based drugs and medications you are recommended to follow the program offered in Ironbound Shelly Manning, an eBook. In this eBook, she has discussed 5 superfoods and other methods to help you in reducing the level of iron in your body in a natural manner. Many people are benefited from this program after following it consistently.