Team 2: Cardiovascular Structural Diseases

Group leaders: Catherine BOILEAU & Guillaume JONDEAU

LdVAortic root and aortic valves share numerous common structural, physiological, genetic, and pathophysiologic features. Aortic root and heart valves are vascular tissues highly enriched with fibrillar insoluble extracellular matrix components, including proteoglycans, elastin, and collagen — in situ synthesized by stromal cells : myofibroblasts in valves, smooth muscle cells in aorta. Both tissues support the elevated mechanical stress generated by hemodynamics in the human body, including physiological vortices in the valsalva sinus during diastole (depicted by Leornardo Da Vinci 500 years ago; figure) and the impact of the systolic ejected flow on the aortic root. As a consequence, aortic root and valves pathologies share common etiologies including monogenic heritable diseases, such as Marfan syndrome, which is recognized as a pathogenic determinant of aneurysms and dissections of the ascending aorta, but also of valve structural abnormality and dysfunction. In parallel, bicuspid aortic valve, a highly frequent congenital anomaly, is an important anatomic risk factor for development of aortic valve stenosis but also of aneurysms and/or dissections of the aortic root. Structural diseases of aortic root, aneurysms and dissections, and heart valves, stenosis and calcifications, share the common histological feature of areas of mucoid degeneration, determined by genomic/ hemodynamic microenvironment in both these tissues. For example, aneurysms preferentially develop in valsalva sinus in response to Marfan mutations, in relation to physiological vortices, whereas aneurysms develop in the aortic root in bicuspids, in relation to the change of the aortic ring geometry (oval versus round).

Our project is to pursue the discovery of new genes and of genetic modifiers involved in aortic root and valve diseases in human, to decipher the common and different pathophysiology of these diseases, to develop new diagnostic (functional and molecular imaging) and interventional therapeutics and to decrypt the interactions between aortic valves and aortic root.

The new team 2 originated from Team 6 of U698 (C Boileau) with the addition for the valvular disease project of D Messika-Zeitoun, Alec Vahanian, B Iung – new members – and D Himbert (PH) and MP Jacob (DR2 CNRS) from previous teams 5 and 2, respectively.

Family name
First name
Position
Tel
Email
ABI-FADELMariannePRmarianne.abi-fadel@inserm.fr
ABOU KHALILYaraDoctorantyara.abou-khalil@inserm.fr
ARNAUDPaulineAHU01.40.25.85.55pauline.arnaud@aphp.fr
AZARYaraDoctorantyara.azar@net.usj.edu.lb
BOILEAUCatherinePUPH101.40.25.75.21catherine.boileau@inserm.fr
EL BITARSandyMCFsandyelbitar@gmail.com
EL KHOURYPetraMCFpetra_khoury@hotmail.com
GHALEBYoumnaMCF01.40.25.75.22youmna.ghaleb@inserm.fr
HANNANadinePH01.49.09.55.97nadine.hanna@aphp.fr
HIMBERTDominiquePH01.40.25.73.25dominique.himbert@aphp.fr
IUNGBernardPUPH1bernard.iung@aphp.fr
JONDEAUGuillaumePUPH101.40.25.68.10guillaume.jondeau@aphp.fr
LE GOFFCarineCR01.40.25.75.21carine.le-goff@inserm.fr
MICHELJean-BaptisteDREM01.40.25.75.26jean-baptiste.michel@inserm.fr
MILLERONOlivierPHolivier.milleron-ext@aphp.fr
MOREIRA FURTADOMelannyM1melannymoreira@gmail.com
MOUGINZakariaDoctorantzakaria.mougin@inserm.fr
PELLENCQuentinDoctorantquentin.pellenc@aphp.fr
RABESJean-PierreMCUPH01.49.09.55.97jean-pierre.rabes@aphp.fr
URENA-ALCAZARMarinaMCUPHmarina.urena-alcazar@aphp.fr
VARRETMathildeCR01.40.25.75.21mathilde.varret@inserm.fr

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Amat-Santos IJ, Messika-Zeitoun D, Eltchaninoff H, Kapadia S, Lerakis S, Cheema AN, Gutiérrez-Ibanes E, Munoz A, Pan M, Webb JG, Herrmann H, Kodali S, Nombela-Franco L, Tamburino C, Jilaihawi H, Masson J-B, Sandoli de Brito F, Cristina Ferreira M, Lima VC, Mangione JA, Iung B, Vahanian A, Durand E, Tuzcu M, Hayek SS, Angulo-Llanos R, Gómez-Doblas JJ, Castillo JC, Dvir D, Leon MB, Garcia E, Cobiella J, Barbanti M, Makkar R, Barbosa Ribeiro H, Urena M, Dumont E, Pibarot P, Lopez J, San Roman A, Rodés-Cabau J. 2015. Response to Letters Regarding Article, “Infective Endocarditis After Transcatheter Aortic Valve Implantation: Results From a Large Multicenter Registry.” Circulation 132:e372-374.
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Amat-Santos IJ, Messika-Zeitoun D, Eltchaninoff H, Kapadia S, Lerakis S, Cheema AN, Gutiérrez-Ibanes E, Munoz-Garcia AJ, Pan M, Webb JG, Herrmann HC, Kodali S, Nombela-Franco L, Tamburino C, Jilaihawi H, Masson J-B, de Brito FSJ, Ferreira MC, Lima VC, Mangione JA, Iung B, Vahanian A, Durand E, Tuzcu EM, Hayek SS, Angulo-Llanos R, Gómez-Doblas JJ, Castillo JC, Dvir D, Leon MB, Garcia E, Cobiella J, Vilacosta I, Barbanti M, R Makkar R, Ribeiro HB, Urena M, Dumont E, Pibarot P, Lopez J, San Roman A, Rodés-Cabau J. 2015. Infective endocarditis after transcatheter aortic valve implantation: results from a large multicenter registry. Circulation 131:1566–1574.
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Arai T, Morice M-C, O’Connor SA, Yamamoto M, Eltchaninoff H, Leguerrier A, Leprince P, Laskar M, Iung B, Fajadet J, Prat A, Lièvre M, Donzeau-Gouge P, Chevreul K, Teiger E, Lefèvre T, Gilard M. 2015. Impact of pre- and post-procedural anemia on the incidence of acute kidney injury and 1-year mortality in patients undergoing transcatheter aortic valve implantation (from the French Aortic National CoreValve and Edwards 2 [FRANCE 2] Registry). Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions 85:1231–1239.
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Amsallem M, Ou P, Milleron O, Henry-Feugeas M-C, Detaint D, Arnoult F, Vahanian A, Jondeau G. 2015. Comparative assessment of ascending aortic aneurysms in Marfan patients using ECG-gated computerized tomographic angiography versus trans-thoracic echocardiography. International journal of cardiology 184:22–27.
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Aubart M, Gross M-S, Hanna N, Zabot M-T, Sznajder M, Detaint D, Gouya L, Jondeau G, Boileau C, Stheneur C. 2015. The clinical presentation of Marfan syndrome is modulated by expression of wild-type FBN1 allele. Human molecular genetics 24:2764–2770.
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Auffret V, Bedossa M, Boulmier D, Verhoye JP, Ruggieri VG, Koning R, Laskar M, Van Belle É, Leprince P, Collet JP, Iung B, Lefèvre T, Eltchaninoff H, Gilard M, Le Breton H. 2015. [From FRANCE 2 to FRANCE TAVI: are indications, technique and results of transcatheter aortic valve replacement the same?]. Presse medicale (Paris, France : 1983) 44:752–760.
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Barbash IM, Barbanti M, Webb J, Molina-Martin De Nicolas J, Abramowitz Y, Latib A, Nguyen C, Deuschl F, Segev A, Sideris K, Buccheri S, Simonato M, Rosa FD, Tamburino C, Jilaihawi H, Miyazaki T, Himbert D, Schofer N, Guetta V, Bleiziffer S, Tchetche D, Immè S, Makkar RR, Vahanian A, Treede H, Lange R, Colombo A, Dvir D. 2015. Comparison of vascular closure devices for access site closure after transfemoral aortic valve implantation. European heart journal 36:3370–3379.
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Bière L, Launay M, Pinaud F, Hamel J-F, Eltchaninoff H, Iung B, Laskar M, Leguerrier A, Gilard M, Furber A. 2015. Influence of sex on mortality and perioperative outcomes in patients undergoing TAVR: insights from the FRANCE 2 registry. Journal of the American College of Cardiology 65:755–757.
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Bouleti C, Fassa A-A, Himbert D, Brochet E, Ducrocq G, Nejjari M, Ghodbane W, Depoix J-P, Nataf P, Vahanian A. 2015. Transfemoral implantation of transcatheter heart valves after deterioration of mitral bioprosthesis or previous ring annuloplasty. JACC Cardiovascular interventions 8:83–91.
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Bouleti C, Himbert D, Brochet E, Ou P, Iung B, Nejjari M, Ghodbane W, Fassa A-A, Depoix J-P, Vahanian A. 2015. Transfemoral tricuspid valve-in-ring implantation using the edwards Sapien XT valve: one-year follow-up. Circulation Cardiovascular interventions 8.
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Bouleti C, Himbert D, Iung B, Alos B, Kerneis C, Ghodbane W, Messika-Zeitoun D, Brochet E, Fassa A-A, Depoix J-P, Ou P, Nataf P, Vahanian A. 2015. Long-term outcome after transcatheter aortic valve implantation. Heart (British Cardiac Society) 101:936–942.
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Burillo E, Lindholt JS, Molina-Sánchez P, Jorge I, Martinez-Pinna R, Blanco-Colio LM, Tarin C, Torres-Fonseca MM, Esteban M, Laustsen J, Ramos-Mozo P, Calvo E, Lopez JA, Vega de Ceniga M, Michel J-B, Egido J, Andrés V, Vazquéz J, Meilhac O, Martin-Ventura JL. 2015. ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression. Thrombosis and haemostasis 113:1335–1346.
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Castellant P, Didier R, Bezon E, Couturaud F, Eltchaninoff H, Iung B, Donzeau-Gouge P, Chevreul K, Fajadet J, Leprince P, Leguerrier A, Lievre M, Prat A, Teiger E, Laskar M, Boschat J, Gilard M. 2015. Comparison of Outcome of Transcatheter Aortic Valve Implantation With Versus Without Previous Coronary Artery Bypass Grafting (from the FRANCE 2 Registry). The American journal of cardiology 116:420–425.
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Clement M, Guedj K, Andreata F, Morvan M, Bey L, Khallou-Laschet J, Gaston A-T, Delbosc S, Alsac J-M, Bruneval P, Deschildre C, Le Borgne M, Castier Y, Kim H-J, Cantor H, Michel J-B, Caligiuri G, Nicoletti A. 2015. Control of the T follicular helper-germinal center B-cell axis by CD8+ regulatory T cells limits atherosclerosis and tertiary lymphoid organ development. Circulation 131:560–570.
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Chopard R, Teiger E, Meneveau N, Chocron S, Gilard M, Laskar M, Eltchaninoff H, Iung B, Leprince P, Chevreul K, Prat A, Lievre M, Leguerrier A, Donzeau-Gouge P, Fajadet J, Mouillet G, Schiele F. 2015. Baseline Characteristics and Prognostic Implications of Pre-Existing and New-Onset Atrial Fibrillation After Transcatheter Aortic Valve Implantation: Results From the FRANCE-2 Registry. JACC Cardiovascular interventions 8:1346–1355.
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Cimadevilla C, Nadia B, Dreyfus J, Perez F, Cueff C, Malanca M, Brochet E, Iung B, Vahanian A, Messika-Zeitoun D. 2015. Echocardiographic measurement of left atrial volume: Does the method matter? Archives of cardiovascular diseases 108:643–649.
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Clerfond G, Pereira B, Innorta A, Motreff P, Gilard M, Laskar M, Eltchaninoff H, Iung B, Leprince P, Teiger E, Chevreul K, Prat A, Lievre M, Leguerrier A, Donzeau-Gouge P, Fajadet J, Souteyrand G. 2015. Comparison of outcomes after one-versus-two transcatheter aortic valve implantation during a same procedure (from the FRANCE2 Registry). The American journal of cardiology 115:1273–1280.
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Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, Kuivenhoven JA, Nordestgaard BG, Descamps OS, Steinhagen-Thiessen E, Tybjaerg-Hansen A, Watts GF, Averna M, Boileau C, Borén J, Catapano AL, Defesche JC, Hovingh GK, Humphries SE, Kovanen PT, Masana L, Pajukanta P, Parhofer KG, Ray KK, Stalenhoef AFH, Stroes E, Taskinen M-R, Wiegman A, Wiklund O, Chapman MJ. 2015. [Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society]. Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir 43 Suppl 1:1–14.
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Gazal S, Sacre K, Allanore Y, Teruel M, Goodall AH, Tohma S, Alfredsson L, Okada Y, Xie G, Constantin A, Balsa A, Kawasaki A, Nicaise P, Amos C, Rodriguez-Rodriguez L, Chiocchia G, Boileau C, Zhang J, Vittecoq O, Barnetche T, Gonzalez Gay MA, Furukawa H, Cantagrel A, Le Loët X, Sumida T, Hurtado-Nedelec M, Richez C, Chollet-Martin S, Schaeverbeke T, Combe B, Khoryati L, Coustet B, El-Benna J, Siminovitch K, Plenge R, Padyukov L, Martin J, Tsuchiya N, Dieudé P. 2015. Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene. Annals of the rheumatic diseases 74:e19.
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Guauque-Olarte S, Messika-Zeitoun D, Droit A, Lamontagne M, Tremblay-Marchand J, Lavoie-Charland E, Gaudreault N, Arsenault BJ, Dubé M-P, Tardif J-C, Body SC, Seidman JG, Boileau C, Mathieu P, Pibarot P, Bossé Y. 2015. Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease. Circulation Cardiovascular genetics 8:812–822.
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Guo D, Gong L, Regalado ES, Santos-Cortez RL, Zhao R, Cai B, Veeraraghavan S, Prakash SK, Johnson RJ, Muilenburg A, Willing M, Jondeau G, Boileau C, Pannu H, Moran R, Debacker J, Bamshad MJ, Shendure J, Nickerson DA, Leal SM, Raman CS, Swindell EC, Milewicz DM. 2015. MAT2A mutations predispose individuals to thoracic aortic aneurysms. American journal of human genetics 96:170–177.
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Himbert D, Vahanian A. 2015. Transcatheter aortic valve replacement for patients with heart failure. Heart failure clinics 11:231–242.
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Iung B, Laouenan C, Vahanian A, Gilard M. 2015. Considerations on the poor discriminatory power of the FRANCE-2 risk score: Authors’ reply. Heart (British Cardiac Society) 101:1170.
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Jiang P, Loyau S, Tchitchinadze M, Ropers J, Jondeau G, Jandrot-Perrus M. 2015. Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan. PloS one 10:e0128744.
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Nguyen C, Cheong AP, Himbert D. 2015. Valve-in-valve-in-valve: Treating endocarditis of a transcatheter heart valve. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions 86:E200-204.
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Obadia J-F, Armoiry X, Iung B, Lefèvre T, Mewton N, Messika-Zeitoun D, Cormier B, Berthiller J, Maucort-Boulch D, Boutitie F, Vaz B, Trochu J-N, Vahanian A. 2015. The MITRA-FR study: design and rationale of a randomised study of percutaneous mitral valve repair compared with optimal medical management alone for severe secondary mitral regurgitation. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 10:1354–1360.
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Plurien F, Bruneval P, Jobic Y, Iung B, Ennezat P-V. 2015. Calcifications in benfluorex-induced valve heart disease: a misknown association. Cardiology 130:87–90.
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Regalado ES, Guo D, Prakash S, Bensend TA, Flynn K, Estrera A, Safi H, Liang D, Hyland J, Child A, Arno G, Boileau C, Jondeau G, Braverman A, Moran R, Morisaki T, Morisaki H, Pyeritz R, Coselli J, LeMaire S, Milewicz DM. 2015. Aortic Disease Presentation and Outcome Associated With ACTA2 Mutations. Circulation Cardiovascular genetics 8:457–464.
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Ruys TPE, Roos-Hesselink JW, Pijuan-Domènech A, Vasario E, Gaisin IR, Iung B, Freeman LJ, Gordon EP, Pieper PG, Hall R, Boersma E, Johnson MR. 2015. Is a planned caesarean section in women with cardiac disease beneficial? Heart (British Cardiac Society) 101:530–536.