Validation of New Therapeutic Targets to Prevent Collagen Accumulation During Cardiac Fibrosis: Procollagen C-proteinase Enhancers

Study Overview
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Brief Summary
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Heart failure is characterized by cardiac fibrosis linked to extracellular collagen deposits. Collagens are synthesized as soluble precursors, procollagens, which must undergo proteolytic maturation to assemble into fibres. This step is under the control of two extracellular proteins, procollagen C-proteinase enhancer 1 and 2 (PCPE-1 and -2). The mechanism of action of these highly effective and specific activators was recently elucidated by one of our partners. Preliminary results, as well as data from the literature, indicate a strong correlation between the expression rates of PCPEs and cardiac fibrosis. The aim of this study is to validate in humans, by analysis of endomyocardial tissue biopsies, the hypothesis that PCPEs contribute to the anarchic accumulation of collagen during cardiac fibrosis and to evaluate the interest of developing new diagnostic and therapeutic strategies for cardiac fibrosis using PCPE agonists.

Official Title
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Validation of New Therapeutic Targets to Prevent Collagen Accumulation During Cardiac Fibrosis: Procollagen C-proteinase Enhancers

Conditions
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Valvulopathy, Heart Surgery, Procollagen C-Proteinase Enhancers

Intervention / Treatment
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* Biological: Biopsies
* Biological: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Person who has given written consent Patient aged 18 to 85 for men and 60 to 85 for women Patient requiring cardiac surgery for aortic valve replacement or aortic plastic surgery or aortic plasty or ascending aorta replacement more or less associated with aortic valve surgery Exclusion Criteria: Person not affiliated or not benefiting from national health insurance Person subject to a measure of legal protection (curatorship, guardianship) Person deprived of liberty, by judicial or administrative decision Major incapable or incapable of giving consent Minor Pregnant or breastfeeding woman Emergency Surgery Acute Infectious Endocarditis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Biopsies|Three endomyocardial intraoperative biopsies were performed on the left ventricle. Resection of the left atrium in the event of atrial fibrillation.|
|Biological: Blood sampling|Pre-operative blood sampling|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial fibrosis rate | Measurement of the level of myocardial fibrosis in myocardial tissue. | Through study completion, an average of 1 year | 
| Rate of PCPE-1/2 | Measurement of PCPE-1/2 rate in myocardial tissue. | Through study completion, an average of 1 year |