Cytokine expression profile of native heart valves obtained from patients with infective endocarditis

Abstract

Infectious endocarditis is characterized by dysfunction of heart valves and contribute significantly to the cardiovascular morbidity and mortality worldwide, especially in low- and middle-income countries. Immune response is playing the important role in the pathophysiology of this disease. This work was aimed to study the local cytokine profile in native heart valves obtained from the patients with infectious endocarditis. Cytokine profiling were performed in biopsies of native heart valves explanted from 4 patients with infective endocarditis (experimental group) and 10 patients with rheumatic heart disease (comparison group) by dot blotting using the Proteome Profiler™ Human Cytokine Array Kit (ARY005B). The results of dot blotting were validated by the gene expression profiling using quantitative polymerase chain reaction. MIF, PAI-1, ICAM-1 and CXCL12 were found in the native heart valves explanted from both infective endocarditis and rheumatic heart disease patients. Upon a semi-quantitative assessment, the heart valves explanted from the infective endocarditis patients were characterized by 4-fold increased secretion of PAI-1 and twofold decreased secretion of ICAM-1 and CXCL12 compared to the heart valves ffected by rheumatic heart disease. MIF was expressed on similar levels in the both studied groups. IL-1ra, IL-6, IL-8, IL-16, CCL4, CCL5 and CXCL1 were detected only in heart valves affected by infectious endocarditis. At the gene expression level, MIF, IL6, IL8 genes were upregulated and PAI1, IL1RA, CXCL1 genes were downregulated in heart valves explanted from infectious endocarditis patients compared to the subjects affected by rheumatic heart disease. Native heart valves in cases of infectious endocarditis are characterized by nonspecific local inflammatory response associated with pathogenic bacteremia, along with active neovascularization. The data obtained can help to better understand fundamental pathogenetic mechanisms of infectious endocarditis.

Keywords

• infectious endocarditis
• native heart valves
• pathogenic bacteremia
• inflammation
• gene expression
• proteomic profile