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Published on: May 12, 2020
Malondialdehyde as an Important Key Factor of Molecular Mechanisms of Vascular Wall Damage under Heart Diseases
Vadim Z Lankin1, Alla K Tikhaze1, Arthur M Melkumyants1
1Department for Free Radical Research, National Medical Research Center of Cardiology, Russian Ministry of Health, 121552 Moscow, Russia.
Abstract:
This mini review is devoted to a specific issue: the role of malondialdehyde (MDA)-a secondary product of free radical lipid peroxidation-in the molecular mechanisms of the formation of primary atherosclerotic vascular wall lesions. The principal difference between this review and the available literature is that it discusses in detail the important role in atherogenesis not of "oxidized" LDL (i.e., LDL particles containing lipohydroperoxides), but of LDL particles chemically modified by the natural low-molecular weight dicarbonyl MDA. To confirm this, we consider the data obtained by us earlier, indicating that "atherogenic" are not LDL oxidized as a result of free radical lipoperoxidation and containing lipohydroperoxy derivatives of phospholipids in the outer layer of particles, but LDL whose apoprotein B-100 has been modified due to the chemical reaction of terminal lysine residue amino groups of the apoB-100 with the aldehyde groups of the MDA (Maillard reaction). In addition, we present our original data proving that MDA injures endothelial glycocalyx that suppress the ability of the endothelium to control arterial tone according to changes in wall shear stress. In summary, this mini review for the first time exhaustively discloses the key role of MDA in atherogenesis.
Insights
Malondialdehyde (MDA), a lipid peroxidation product, plays a key role in atherogenesis. It modifies LDL particles and damages endothelial glycocalyx, contributing to arterial lesions.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Pathology
Background:
- Atherosclerosis involves vascular wall lesions.
- Lipid peroxidation produces secondary products like malondialdehyde (MDA).
- Low-density lipoprotein (LDL) modification is central to atherogenesis.
Purpose of the Study:
- To elucidate the role of MDA in the molecular mechanisms of early atherosclerotic lesion formation.
- To differentiate the atherogenic effects of MDA-modified LDL from oxidized LDL.
Main Methods:
- Review of existing literature on lipid peroxidation and atherogenesis.
- Analysis of original data on LDL modification by MDA.
- Investigation of MDA's impact on endothelial glycocalyx and arterial tone regulation.
Main Results:
- LDL particles chemically modified by MDA, not just "oxidized" LDL, are atherogenic.
- MDA modifies apoprotein B-100 via Maillard reaction with lysine residues.
- MDA damages endothelial glycocalyx, impairing arterial tone control.
Conclusions:
- Malondialdehyde (MDA) is a critical factor in atherogenesis.
- MDA-induced LDL modification and endothelial dysfunction are key molecular mechanisms.
- This review highlights MDA's central role, distinct from oxidized LDL effects.
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