Expression of Sodium-glucose Co-transporter 2 in Human Heart

Study Overview
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Brief Summary
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The aim of the study is to evaluate the expression of Sodium Glucose Co-transporter 2 (SGLT2) in myocardium from patients with aortic stenosis. 2 groups of patients will be defined: Group A with diastolic heart failure and Group B without heart failure. The expression of SGLT2 will be measured on small myocardium specimens harvested during aortic valve replacement operation. This study should allow us to better understand the effect of glifozines in human heart failure.

Official Title
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Expression of Sodium Glucose Co-transporter2 in Myocardium From Patients With Aortic Valve Stenosis and With/Without Diastolic Heart Failure

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Biological: Myocardium biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults over 18 years-old Patient with surgical aortic valve stenosis, with or without heart failure, in two equal-sized groups (40 subjects in each group) Subjects affiliated with a social security health insurance plan Subject able to understand the objectives and risks of the research and to give dated and signed informed consent Exclusion Criteria: Infective endocarditis in aortic stenosis Severe coronary pathology associated with aortic stenosis Impossible to give the subject informed information (subject in emergency situation, difficulties in understanding the subject, ...) Subject under legal protection Subject under guardianship or curatorship Pregnancy and/or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patients with aortic valve stenosis with heart failure<br> | Biological: Myocardium biopsy<br>* The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis<br>|
| Experimental: patients with aortic valve stenosis without heart failure<br> | Biological: Myocardium biopsy<br>* The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study the expression levels of SGLT2 in the myocardium of patients with surgical aortic stenosis | Measure of SGLT2 expression level by RT-PCR and | Day 0 | 
| To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis | SGLT2 expression level by immunofluorescence labeling | Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of SGLT2 expression levels between heart failure and non-heart failure patients. | SGLT2 expression levels between the 2 groups of patients | Day 0 | 
| Assess oxidative stress | Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE) | Day 0 | 
| Evaluate the pro-inflammatory response by analysing the expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1 | Pro-inflammatory response: (VCAM-1, ICAM-1, MCP-1). Expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1 by RT-PCR, Western blot analysis and immunofluorescence labeling | Day 0 | 
| Evaluate the pro-fibrotic response | Pro-fibrotic response: TGF beta, Ang II, AT1R, ACE, collagen; MMP-2, MMP-9. Expression level of molecules involved in tissue remodeling TGF beta, Ang II, AT1R, ACE, collagen, MMP-2, MMP-9 by RT-PCR, Western blot analysis and immunofluorescence labeling | Day 0 | 
| Evaluate the pro-senescent response | Pro-senescent response: SA-beta-galactosidase activity, p53, p21, P16. Determination of senescence-associated beta-galactosidase activity on cardiac muscle cryosections, and expression level of senescence mediators p53, p21, p16 by RT-PCR, Western blot analysis and immunofluorescence labeling | Day 0 | 
| Evaluate the pro-thrombotic response | Pro-thrombotic response: tissue factor. Expression level of coagulation cascade activator, tissue factor by RT-PCR, Western blot analysis and immunofluorescence labeling | Day 0 | 
| Evaluate endothelial dysfunction | Endothelial response: eNOS, NO, nitrotyrosine. Expression level of eNOS and nitrotyrosine by RT-PCR, Western blot analysis and immunofluorescence labeling and NO formation using the NO-sensitive fluorescent probe, DAF-FM on heart muscle cryosections | Day 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human heart, myocardium, aortic valve stenosis, heart failure, sodium glucose cotransporter 2