Expression of Sodium-glucose Co-transporter 2 in Human Heart
- Conditions
- Aortic Valve Stenosis
- Interventions
- Biological: Myocardium biopsy
- Registration Number
- NCT05830760
- Lead Sponsor
- University Hospital, Strasbourg, France
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 80
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description patients with aortic valve stenosis without heart failure Myocardium biopsy - patients with aortic valve stenosis with heart failure Myocardium biopsy -
- Primary Outcome Measures
Name Time Method To study the expression levels of SGLT2 in the myocardium of patients with surgical aortic stenosis Day 0 Measure of SGLT2 expression level by RT-PCR and
To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis Day 0 SGLT2 expression level by immunofluorescence labeling
- Secondary Outcome Measures
Name Time Method Evaluate the pro-thrombotic response Day 0 Pro-thrombotic response: tissue factor. Expression level of coagulation cascade activator, tissue factor by RT-PCR, Western blot analysis and immunofluorescence labeling
Evaluate the pro-inflammatory response by analysing the expression level of tissue activation molecules VCAM-1, ICAM-1, MCP-1 Day 0 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
Evaluate the pro-senescent response Day 0 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
Evaluate endothelial dysfunction Day 0 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
Comparison of SGLT2 expression levels between heart failure and non-heart failure patients. Day 0 SGLT2 expression levels between the 2 groups of patients
Assess oxidative stress Day 0 Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)
Evaluate the pro-fibrotic response Day 0 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
Trial Locations
- Locations (1)
Hôpitaux Universitaires de Strasbourg
🇫🇷Strasbourg, France