Infective Endocarditis Clinical Trial
Official title:
Gender Study on Predisposition to Infectious Endocarditis
To evaluate the gender-related elements, a first step will be to analyze the impact of sex ratio on different parameters such as age in endocarditis and the type of underlying valvulopathy and other associated comorbidities.
Numerous epidemiological studies have made it possible to highlight the impact of the genus
on the occurrence and natural evolution of numerous valvulopathies. Severe valve leakage
occurs more frequently in men. This association is also observed in patients with aortic
bicuspid infarction where infective endocarditis (IE) is 3 times more common in men with a
sex ratio of 9 to 2 to 1. Male sex is also a risk factor of AEs in the admission score used
in initial patient management used to stratify the risk of AE and start probabilistic
antibiotic therapy. Several hypotheses were evoked and none made it possible to understand
the impact of sex on the risk of IE. The transcriptome study of IE patients revealed 2
potential biomarkers. S100A11 (S100 calcium binding protein A11) is a diagnostic marker and
AQP9 (Aquaporin 9 gene) a poor prognostic factor in patients with AE. Coxiella burnetii AE is
more common and more severe in humans. A study in the C57 / BL6 mouse demonstrated the role
of 17 beta-estradiol in decreasing bacterial load and granuloma formation in female mice. The
hypothesis formulated is that sex hormones play a role in the natural history of IS. This
hypothesis was confirmed at the transcriptome level in mice and allowed to identify
transcriptomic signatures according to sex; male mice with a more marked inflammatory
response to C. burnetii. In order to evaluate the gender-related elements, an initial work
will be to analyze the impact of sex ratio on different parameters such as age in
endocarditis and the type of underlying valvulopathy and other associated comorbidities.
The second part of the project will study (i) the transcriptional profile of the native
valves removed in patients with endocarditis-free valvulopathy in male and female subjects
(ii) the transcriptional profile of native valves removed during endocarditis in matching sex
underlying valvulopathy and microorganism. This will evaluate a possible difference in
susceptibility to endocardial fixation. (iii) the transcriptional profile of PBMCs
(circulating mononuclear cells) in this same patient, which will make it possible to study
the transcriptional profile of the circulating genes and to evaluate the possible difference
in predisposition to endocardial fixation.
Finally, the third part will focus on the histological analysis of the valves collected to
study the differences between man and woman (local inflammatory reaction, cell type found).
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