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

University Hospital, Strasbourg, France

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Conditions

Aortic Valve Stenosis

Interventions

Myocardium biopsyBIOLOGICAL

The expression of SGLT2 on small myocardium specimens harvested during aortic valve replacement operation in patients with aortic stenosis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

Outcomes

Primary Outcomes

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

Time frame: Day 0

To study the SGLT2 tissue localization in the myocardium of patients with surgical aortic stenosis

SGLT2 expression level by immunofluorescence labeling

Time frame: Day 0

Secondary Outcomes

Comparison of SGLT2 expression levels between heart failure and non-heart failure patients.

SGLT2 expression levels between the 2 groups of patients

Time frame: Day 0

Assess oxidative stress

Pro-oxidant response (fluorescence level of the redox-sensitive fluorescent probe DHE)

Time frame: 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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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