Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress

Abstract

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.

Keywords: atherosclerotic cardiovascular diseases; infectious agents; oxidative stress.

Figure 1

Putative pathways of infectious agent-mediated oxidative stress in several stages of the atherosclerotic process. C. pneumoniae, HIV, HCV, HSV, and CMV contribute to endothelial dysfunction; P. gingivalis, A. actinomycetemcomitans, C. pneumoniae, HIV, HCV, and CMV trigger LDL oxidation; P. gingivalis, C. pneumoniae, and CMV induce macrophage-derived foam cell formation; P. gingivalis, C. pneumoniae, HSV, and CMV contribute to progression of atherosclerotic plaque (ICAM: intercellular adhesion molecule; NOX: nicotinamide adenine dinucleotide phosphate oxidase; MPO: myeloperoxidase; NOS: nitric oxide synthase; COX-2: cyclooxygenase-2; LPO: lipoxygenase).