MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta
- Conditions
- Aortic Aneurysm and Dissection
- Interventions
- Other: Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases
- Registration Number
- NCT05434481
- Lead Sponsor
- University Hospital, Angers
- Brief Summary
The main objective is to compare the mitochondrial dynamic between patients operated for aneurysm of ascending aorta or type A aortic dissection (AAD) or control group
- Detailed Description
In an aortic aneurysm process, the alteration of the extracellular matrix (ECM) as well as the apoptosis of the smooth muscle cells are due to inflammatory phenomena and oxydative stress, involving mitochondria which has a key place within cells.
Mitochondrial fusion and fission constitute mitochondrial dynamic and are involved in the mechanisms described above.
The alteration of mitochondrial dynamics has been demonstrated in many pathologies, in particular neurological, cancer and cardiovascular disease and generally occurs in favor of fission.
In a mouse model (FASEB J, 2021, Robert P ), the role of mitochondrial fusion has been demostrated as a protective factor against hypertension in resistance arteries and a deletion of OPA1 (optic Atrophy 1) fusion protein may lead to aneurysm until aortic dissection. The results of this experimental study suggest a role of the alteration of mitochondrial dynamic in the development of aneurysm and aortic dissection.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 60
- Aneurysm aortic group: patients treated for an aneurysm of the ascending thoracic aorta with surgical indication according to the ESC guidelines (2014).
- Aortic dissection group: patients treated for type A acute aortic dissection or intramural hematoma of the ascending thoracic aorta in emergency.
- Control group: patients operated for aortic valve replacement (little aortic sample before closing aortotomy) or coronary artery bypass grafting which the use of a saphenous graft and the performance of a proximal anastomosis on the ascending aorta is planned
- Patients under 18 years old
- Other acute aortic syndromes (penetrating ulcers, iatrogenic or traumatic dissections)
- Patients treated for aortic valve replacement in the context of infective endocarditis
- Patients treated for emergency aortic valve replacement or coronary bypass surgery**
- Pregnant, parturient and breastfeeding women
- Patients protected by an administrative or judicial measure (curatorship, guardianship)
- Patients receiving psychiatric care under duress
- Adults subject to a legal protection measure.
- Patients whose the samples planned for the study could not be taken;
- Patients in the control group whose tissue sampling will not be performed.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control group Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases Patients without aortic aneurysm or aortic dissection operated for aortic valve replacement (AVR) and/or coronary artery bypass with a saphenous vein graft for proximal aortic anastomosis to collect the aortic sample. For patients operated for AVR, an aortic sample will be collected before closing the aorta. Type A aortic dissection group Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases Patients operated for type A aortic dissection according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014). Aneurysm group Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases Patients operated for aneurysm of the ascending aorta according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014).
- Primary Outcome Measures
Name Time Method Level of tissue expression of the genes and coding for the proteins MFN2 (Mitofusin 2) 1 month Level expression of MFN2 (Mitofusin 2) by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Nfr1 1 month Level expression of Nfr1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Fis1 1 month Level expression of Fis1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins MFN1 (Mitofusin 1) 1 month Level expression of MFN1 (Mitofusin 1) by RT-qPCR
Level of tissue expression of the genes and coding for the proteins (Optic Atrophy 1) OPA1 1 month Level expression of, (Optic Atrophy 1) OPA1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Drp1 1 month Level expression of Drp1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Tfam 1 month Level expression of Tfam by RT-qPCR
Level of tissue expression of the genes and coding for the proteins PGC1⍺ 1 month Level expression of PGC1⍺ by RT-qPCR
Analysis of mitochondrial network 1 month To analyze the mitochondrial network, vascular smooth muscle cells will be extracted from the wall of aorta samples and seeded in Petri dish. When 80% confluence is obtained, cells will be incubated with a green fluorescent marker (Mitotacker Green Probes) and 3D fluorescence microscopy will be used. Analysis of mitochondrial network will be done after characterization of mitochondrial shapes and distribution in the different aorta samples.
- Secondary Outcome Measures
Name Time Method Proteins of Smooth Muscle Cell reactivity: Myh11 1 month Level expression of Myh11 by western blot
Protein of remodelling and constitution of extracellular matrix: Metalloprotease MMp2 1 month Level expression of Metalloprotease MMp2 by western blot
Proteins of remodelling and constitution of extracellular matrix: Collagene I/III 1 month. Level expression of Collagene I/III by western blot
Protein of remodelling and constitution of extracellular matrix: Elastine 1 month Level expression of Elastine by western blot
Proteins of remodelling and constitution of extracellular matrix: Timp 1/2 1 month Level expression of Timp 1/2 by western blot
Proteins of oxydative stress: Sod 1/2 1 month Level expression of Sod 1/2 by western blot
Proteins of survival cell: Bcl2/Bax 1 month Level expression of Bcl2/Bax by western blot
Proteins of survival cell: Cytochrome C 1 month Level expression of Cytochrome C by western blot
Proteins of oxydative stress: NADPH 1 month Level expression of NADPH by western blot
Proteins of oxydative stress: OxyD 1 month Level expression of OxyD by western blot
Analysis of Aorta Metabolomes 2 years 136 metabolites will be measured in plasma samples. Plasma data blocks will be submitted to multiblock orthogonal component analysis (MOCA) after normalizing concentrations of aorta samples by their weights.
Analysis of Plasma Metabolomes 2 years 154 metabolites will be measured in plasma samples. Plasma data blocks will be submitted to multiblock orthogonal component analysis (MOCA) after normalizing concentrations of plasma samples by their weights.
Proteins of Smooth Muscle Cell reactivity: Acta 2 1 month Level expression of Acta 2 by western blot
Proteins of Smooth Muscle Cell reactivity: MLC20 1 month Level expression of MLC20 by western blot
Proteins of Smooth Muscle Cell reactivity: Rock1 1 month Level expression of Rock1 by western blot
Proteins of Smooth Muscle Cell reactivity: Rhoa 1 month Level expression of Rhoa by western blot
Trial Locations
- Locations (1)
Olivier FOUQUET
🇫🇷Angers, France