Infections, atherosclerosis, and coronary heart disease

Abstract

Atherosclerosis is a chronic inflammatory disease. Pathophysiological similarities between chronic infections and atherosclerosis triggered interest in a clinical association between these conditions. Various infectious microbes have been linked to atherosclerotic vascular disease in epidemiological studies. However, this association failed to satisfy the Koch's postulates of causation with multiple clinical trials demonstrating inefficacy of anti-infective therapies in mitigating atherosclerotic cardiovascular events. Identification of underlying pathophysiological mechanisms and experience with vaccination against various infectious agents has ushered a new avenue of efforts in the development of an anti-atherosclerotic vaccine. Studies in animal models have identified various innate and adaptive immune pathways in atherosclerosis. In this review, we discuss the patho-biological link between chronic infections and atherosclerosis, evaluate existing evidence of animal and human trials on the association between infections and cardiovascular disease and introduce the concept of an anti-atherosclerotic vaccine.

G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

“…Clinical reports have revealed a possible association of viral infections with atherosclerosis in humans, which was subsequently confirmed in mice (16). It has been proposed that infection modulates atherosclerosis progression by inducing substantial pathologic changes, such as oxidative stress and ER stress, in local endothelial cells, in smooth muscle cells and in immune (mainly T) cells (17,18). In addition, genetic variants of TLR4, the major receptor of LPS, were clinically associated with cardiovascular diseases, further supporting the role of inflammation in atherosclerosis (19).…”

Beneficial Effects of Vaccination on Cardiovascular Events: Myocardial Infarction, Stroke, Heart Failure

“…Infections, as a stimulus of inflammation, have long been linked to the genesis, progression and instability of atherosclerotic plaques [24]. Multiple infectious agents, including influenza, have been shown to induce local pro-atherosclerotic mechanisms, such as expression of adhesion molecules, production of monocyte chemoattractant protein-1, oxidation of LDL, that lead to activation of endothelium, migration of leucocytes and eventually formation of lipid core [24-27].…”

“…Multiple infectious agents, including influenza, have been shown to induce local pro-atherosclerotic mechanisms, such as expression of adhesion molecules, production of monocyte chemoattractant protein-1, oxidation of LDL, that lead to activation of endothelium, migration of leucocytes and eventually formation of lipid core [24-27]. Infections have also been associated with increased smooth muscle cell proliferation in the vessel wall that contributes to plaque progression [24]. In an animal model of atherosclerosis, it has been shown that influenza infection promotes inflammation, smooth muscle cell proliferation, and fibrin deposition in atherosclerotic plaques, similar to unstable plaques after MI [28].…”

“…Numerous mechanisms support a causal association between acute respiratory infection and CV events: an increase in pro-inflammatory, prothrombotic cytokines, endothelial dysfunction, stimulation of platelet activity, increased shear force, induction of procoagulant activity and inhibition of anticoagulant mechanisms, reduction in the clotting time, increase in the expression of tissue factor, increased plasma viscosity, loss of the anti-inflammatory properties of HDL particles, increase in trafficking of macrophages into the arterial wall, release of endogenous catecholamines, tachycardia, psychological distress, dehydration, hypoxemia [6, 7, 24]. The protective effect of vaccination is associated with the prevention of respiratory infections and the associated stresses [6, 18].…”

“…The biggest challenge in this regard has been the identification of antigens that could play the role of targets for immunomodulatory therapy. Apart from vaccinations against exogenous infectious antigens described earlier, there are several studies exploring vaccinations against endogenous antigens, such as LDL and Apo-B, which may hold promise [16, 24, 74]. …”