Cellular and Molecular Profiling of Native Heart Valves in Infective Endocarditis: A Comparative Study with Calcific...

Area of Science:

• Cardiovascular Pathology
• Molecular Biology
• Immunology

Background:

• Infective endocarditis (IE) impacts native and prosthetic heart valves, endocardial surfaces, and cardiac devices.
• Early risk stratification biomarkers for IE are critical, especially for blood culture-negative cases.
• Understanding IE pathogenesis requires detailed analysis of affected heart valve tissues.

Purpose of the Study:

• To investigate cellular and molecular differences in native heart valves between IE and calcific aortic valve disease (CAVD) patients.
• To identify potential biomarkers for early risk stratification of IE.
• To elucidate the pathogenesis of IE in native heart valves.

Main Methods:

• Immunohistochemical analysis of leukocyte, macrophage, lymphocyte, neutrophil, and endothelial cell markers (CD45, CD68, CD3, CD19, MPO, CD31).
• Whole-transcriptome sequencing to identify differentially expressed genes (DEGs).
• Proteomic profiling using dot-blotting to analyze cytokine, protease, and enzyme inhibitor expression.

Main Results:

• IE-affected valves showed infiltration of macrophages, neutrophils, and T-lymphocytes; CAVD valves lacked neutrophils.
• Whole-transcriptome sequencing revealed 157 DEGs (124 upregulated, 33 downregulated) in IE valves versus CAVD valves.
• Proteomic analysis identified 35 cytokines, 13 proteases, and 18 enzyme inhibitors, with distinct expression patterns between IE and CAVD.

Conclusions:

• The study provides insights into the pathogenesis of infective endocarditis.
• Candidate cellular (macrophages, neutrophils) and molecular-genetic features of IE-affected native heart valves were identified.
• These findings may contribute to improved early risk stratification and diagnosis of IE.