The role of infection and immunity in atherosclerosis

Abstract

Cardiovascular diseases account for 20% of deaths worldwide, rising to 50% in developed countries. Current understanding of atherosclerosis derives from a combination of research in animals and cell cultures, analysis of human lesions, clinical investigations of patients with acute coronary syndromes and epidemiological studies of coronary artery disease. By measuring serologic titers in the serum of patients after cardiovascular events, it was observed that the greater the infectious exposure of a patient, the larger the atherosclerotic lesion extension. In addition, gene targeting or pharmacological inhibition of certain cytokines aggravates atherosclerosis in animal experiments. Other animal experiments have succeeded in proving that B cells play a protective role in atherosclerosis through induced immunity against oxidized low-density lipoprotein and other epitopes. Molecular mimicry might respond to the question of how infection may trigger vulnerability in previously stable atherosclerotic lesions. The FLU Vaccination Acute Coronary Syndromes trial enhanced the debate on atherosclerosis prevention by the application of antiflu vaccine. So far, antibiotics have failed to reduce cardiovascular risk, as recent trials could not demonstrate a statistically significant risk reduction. Having assumed atherosclerosis to be an inflammatory disease, the WHO considered the possible role of secondary prevention with antiflu vaccine.

Identifying patterns of immune-related disease: use in disease prevention and management

“…1 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and 2 [37][38][39][40][41][42][43][44][45][46][47][48][49][50] . These include: 1) allergy; 2) autoimmunity; 3) infl ammation; and 4) infection.…”

“…Colorectal cancer [43] Multiple sclerosis [37] Autoimmune hepatitis [38] Asthma [39] Polyneuropathy [41] Pediatric deep vein thrombosis [40] Ankylosing spondylitis [37] Depression [42] An infection-related disease patterns Asthma [45] Otitis media [44] Chronic bronchitis [45] Atherosclerosis [46] Lung cancer [48] Adult snoring [49] Secondary bacterial infections [50] Infant respiratory infection/rhinitis…”

Prevention of myocardial infarction

“…Once the immune system has had contact with heatshock proteins, induced initially by contact with pathogens, subsequent presentation of these antigens may be followed by a greater immunologic reaction and endothelial dysfunction. Consequently, the repeated aggression of oxidized LDL perpetuates the cycle by recruiting immune cells that are already competent due to first exposure to heat-shock proteins [30 ].…”

“…The final result leads to suppression of plaque inflammatory burst after immunization, which might be documented by reduced expression of cytokines generated by Th1 lymphocytes [30 ]. A different approach to antiatherosclerotic vaccines is transcription and inclusion of a chimeric polypeptide of tetanus toxic T-cell epitope and a cholesteryl ester transfer protein (CETP) B-cell epitope expressed as inclusion bodies in Escherichia coli through genetic manipulation techniques [31].…”

The Effect of Atorvastatin Treatment on Lipid Profile and Adhesion Molecule Levels in Hypercholesterolemic Patients: Relation to Low-Density Lipoprotein Receptor Gene Polymorphism

“…The impairment of ligand-receptor interaction caused by mutations within the LDLR gene occurs as a result of the disturbances in gene expression and/or LDLR structure and leads to congenital abnormalities in cholesterol metabolism, known as familial hypercholesterolemia (FH). Monogenic hypercholesterolemia is one of most common diseases and is inherited as an autosomal dominant disorder [14, 15]. So far, no clear association has been reported between specific mutation/polymorphism and risk of future CAD [16].…”