MITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Level of tissue expression of the genes and coding for the proteins MFN2 (Mitofusin 2)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Level of tissue expression of the genes and coding for the proteins MFN2 (Mitofusin 2)
时间窗: 1 month
Level expression of MFN2 (Mitofusin 2) by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Nfr1
时间窗: 1 month
Level expression of Nfr1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Fis1
时间窗: 1 month
Level expression of Fis1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins MFN1 (Mitofusin 1)
时间窗: 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
时间窗: 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
时间窗: 1 month
Level expression of Drp1 by RT-qPCR
Level of tissue expression of the genes and coding for the proteins Tfam
时间窗: 1 month
Level expression of Tfam by RT-qPCR
Level of tissue expression of the genes and coding for the proteins PGC1⍺
时间窗: 1 month
Level expression of PGC1⍺ by RT-qPCR
Analysis of mitochondrial network
时间窗: 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.
次要结局
- Proteins of Smooth Muscle Cell reactivity: Myh11(1 month)
- Protein of remodelling and constitution of extracellular matrix: Metalloprotease MMp2(1 month)
- Proteins of remodelling and constitution of extracellular matrix: Collagene I/III(1 month.)
- Protein of remodelling and constitution of extracellular matrix: Elastine(1 month)
- Proteins of remodelling and constitution of extracellular matrix: Timp 1/2(1 month)
- Proteins of oxydative stress: Sod 1/2(1 month)
- Proteins of survival cell: Bcl2/Bax(1 month)
- Proteins of survival cell: Cytochrome C(1 month)
- Proteins of oxydative stress: NADPH(1 month)
- Proteins of oxydative stress: OxyD(1 month)
- Analysis of Aorta Metabolomes(2 years)
- Analysis of Plasma Metabolomes(2 years)
- Proteins of Smooth Muscle Cell reactivity: Acta 2(1 month)
- Proteins of Smooth Muscle Cell reactivity: MLC20(1 month)
- Proteins of Smooth Muscle Cell reactivity: Rock1(1 month)
- Proteins of Smooth Muscle Cell reactivity: Rhoa(1 month)