Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Abstract

Although oxidative stress has been long associated with the genesis and progression of the atherosclerotic plaque, scanty data on its in situ effects on protein sulfhydryl group modifications are available. Within the arterial wall, protein sulfhydryls and low-molecular-weight (LMW) thiols are involved in the cell regulation of both Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) levels and are a target for several posttranslational oxidative modifications that take place inside the atherosclerotic plaque, probably contributing to both atherogenesis and atherosclerotic plaque progression towards complicated lesions. Advanced carotid plaques are characterized by very high intraplaque GSH levels, due to cell lysis during apoptotic and/or necrotic events, probably responsible for the altered equilibrium among protein sulfhydryls and LMW thiols. Some lines of evidence show that the prooxidant environment present in atherosclerotic tissue could modify filtered proteins also by protein-SH group oxidation, and demonstrate that particularly albumin, once filtered, represents a harmful source of homocysteine and cysteinylglycine inside the plaque. The oxidative modification of protein sulfhydryls, with particular emphasis to protein thiolation by LMW thiols and its association with atherosclerosis, is the main topic of this review.

Figure 1

Overview of the wide variety of biochemical modifications that reduced protein sulfhydryl groups may potentially undergo. R-SH or LMW thiols: γGlu-Cys-Gly (γglutamyl-cysteinil-glycine, glutathione), Cys (cysteine), HCy (homocysteine), Cys-Gly (cysteine-glycine), and Glu-Cys (glutamyl-cysteine).

Figure 2

Levels of LMW thiols extracted from both circulating and plaque-filtered HSA, expressed as pmoles/pmoles of albumin, obtained by CE-LIF analysis (from [75]). ^∗Significant differences between the two HSA forms (P < 0.001). Cys-Gly: cysteine-glycine; HCy: homocysteine; Cys: cysteine; GSH: glutathione; Glu-Cys: glutamylcysteine.