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| Name | Class |
|---|---|
| Fondation de l'Avenir | OTHER |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aneurysm group | Active Comparator | Patients operated for aneurysm of the ascending aorta according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014). |
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| Type A aortic dissection group | Active Comparator | Patients operated for type A aortic dissection according the guidelines on the diagnosis and treatment of aortic diseases (European Society of Cardiology - 2014). |
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| Control group | Sham Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mitochondrial dynamic analysis in the aorta samples and metabolomic profiling in the aortic diseases | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Level of tissue expression of the genes and coding for the proteins (Optic Atrophy 1) OPA1 | Level expression of, (Optic Atrophy 1) OPA1 by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins MFN1 (Mitofusin 1) | Level expression of MFN1 (Mitofusin 1) by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins MFN2 (Mitofusin 2) | Level expression of MFN2 (Mitofusin 2) by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins Fis1 | Level expression of Fis1 by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins Drp1 | Level expression of Drp1 by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins Nfr1 | Level expression of Nfr1 by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins Tfam | Level expression of Tfam by RT-qPCR | 1 month |
| Level of tissue expression of the genes and coding for the proteins PGC1⍺ |
| Measure | Description | Time Frame |
|---|---|---|
| Protein of remodelling and constitution of extracellular matrix: Metalloprotease MMp2 | Level expression of Metalloprotease MMp2 by western blot | 1 month |
| Proteins of remodelling and constitution of extracellular matrix: Timp 1/2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Olivier FOUQUET | Angers | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28278231 | Background | Trabado S, Al-Salameh A, Croixmarie V, Masson P, Corruble E, Feve B, Colle R, Ripoll L, Walther B, Boursier-Neyret C, Werner E, Becquemont L, Chanson P. The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age. PLoS One. 2017 Mar 9;12(3):e0173615. doi: 10.1371/journal.pone.0173615. eCollection 2017. | |
| 34133045 |
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The data will be collected in a coded manner: first letter of the surname, first letter of the patient's first name, serial number of inclusion in the center by the physicians investigating the study in the electronic observation notebook managed by the DRCI of University Hospital of Angers
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| ID | Term |
|---|---|
| D000784 | Aortic Dissection |
| ID | Term |
|---|---|
| D000094665 | Dissection, Blood Vessel |
| D000783 | Aneurysm |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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Aneurysm and Dissection of Ascending Thoracic Aorta
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|
Level expression of PGC1⍺ by RT-qPCR |
| 1 month |
| Analysis of mitochondrial network | 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. | 1 month |
Level expression of Timp 1/2 by western blot
| 1 month |
| Proteins of remodelling and constitution of extracellular matrix: Collagene I/III | Level expression of Collagene I/III by western blot | 1 month. |
| Protein of remodelling and constitution of extracellular matrix: Elastine | Level expression of Elastine by western blot | 1 month |
| Proteins of survival cell: Bcl2/Bax | Level expression of Bcl2/Bax by western blot | 1 month |
| Proteins of survival cell: Cytochrome C | Level expression of Cytochrome C by western blot | 1 month |
| Proteins of oxydative stress: NADPH | Level expression of NADPH by western blot | 1 month |
| Proteins of oxydative stress: OxyD | Level expression of OxyD by western blot | 1 month |
| Proteins of oxydative stress: Sod 1/2 | Level expression of Sod 1/2 by western blot | 1 month |
| Proteins of Smooth Muscle Cell reactivity: Myh11 | Level expression of Myh11 by western blot | 1 month |
| Proteins of Smooth Muscle Cell reactivity: Acta 2 | Level expression of Acta 2 by western blot | 1 month |
| Proteins of Smooth Muscle Cell reactivity: MLC20 | Level expression of MLC20 by western blot | 1 month |
| Proteins of Smooth Muscle Cell reactivity: Rock1 | Level expression of Rock1 by western blot | 1 month |
| Proteins of Smooth Muscle Cell reactivity: Rhoa | Level expression of Rhoa by western blot | 1 month |
| Analysis of Plasma Metabolomes | 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. | 2 years |
| Analysis of Aorta Metabolomes | 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. | 2 years |
| Robert P, Nguyen PMC, Richard A, Grenier C, Chevrollier A, Munier M, Grimaud L, Proux C, Champin T, Lelievre E, Sarzi E, Vessieres E, Henni S, Prunier D, Reynier P, Lenaers G, Fassot C, Henrion D, Loufrani L. Protective role of the mitochondrial fusion protein OPA1 in hypertension. FASEB J. 2021 Jul;35(7):e21678. doi: 10.1096/fj.202000238RRR. |
| 17850909 | Result | Toda M, Yamamoto K, Shimizu N, Obi S, Kumagaya S, Igarashi T, Kamiya A, Ando J. Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. J Biotechnol. 2008 Jan 20;133(2):239-44. doi: 10.1016/j.jbiotec.2007.08.009. Epub 2007 Aug 9. |
| 24304053 | Result | Archer SL. Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med. 2013 Dec 5;369(23):2236-51. doi: 10.1056/NEJMra1215233. No abstract available. |
| 22406748 | Result | Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, Huynh le H, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F. Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res. 2012 Jun 1;94(3):408-17. doi: 10.1093/cvr/cvs117. Epub 2012 Mar 8. |
| 27723783 | Result | Le Page S, Niro M, Fauconnier J, Cellier L, Tamareille S, Gharib A, Chevrollier A, Loufrani L, Grenier C, Kamel R, Sarzi E, Lacampagne A, Ovize M, Henrion D, Reynier P, Lenaers G, Mirebeau-Prunier D, Prunier F. Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. PLoS One. 2016 Oct 10;11(10):e0164066. doi: 10.1371/journal.pone.0164066. eCollection 2016. |
| D000094683 |
| Acute Aortic Syndrome |
| D001018 | Aortic Diseases |