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    CARFI CARdiovascular Function In vitro



    Platform for the investigation of vascular reactivity


    Numerous platforms offer cardiovascular studies with ultrasound analysis, histological or biochemical measurements. Much less offer analysis of vascular functions large artery such as the aorta and none offers functional study of the small resistance arteries. Thus, based on the expertise of BNMI in the analysis of vascular function in resistance arteries we have mounted a plateform for vascular exploration of small arteries: analysis of vascular reactivity in vitro and in vivo with 3 axes.

    •    Vascular functions and structure in small animals (mice and rats):

    •  Analysis of vascular functions and structure in animal models of human diseases 

    •  Use of endothelium-dependent dilatation as a test for the study of antioxidant and antidiabetic substances (actually plants extracts and derivatives).


    •  Vascular functions and structure in human small blood vessels:

    •  Analysis of vascular functions (endothelium and smooth muscle) and structure

    •  Inclusion of tissues and data in the local data base (CRB)


    • Vascular phenotyping of the whole kidney:

    • Analysis of vascular functions (endothelium and smooth muscle) and structure.

    • Analysis of the effuent (ELISA / cytokines, NOx measurements…etc)


    daniel.henrion @ univ-angers.fr

    Research topics

    Research / expertise topics

    CARFI aims to provide standardized high-quality data on vascular reactivity in vitro.


    Technology available:

    • Telemetry for rats and mice (DSI)
    • Tail cuff for rats and mice (DSI)
    • Arterial catheterisation technique for invasing monitoring (blood pressure, Millar)
    • Flowmeter transonic for arterial blood flow measurements  in arteries in vivo (Emka)
    • Pressure myograph (LSI, Burlington, VT)
    • Four-channel wire myograph (Danis Myotech, DK)






    Service delivery

    In vivo experiments :


    • Tail cuff blood pressure measurement:

    This simple method is realized on vigils animals, slightly constrained. This simple method of reference is to determine the minimum pressure against able to stop arterial blood flow by inflating a cuff around the tail. This non-invasive method for examining animals without an anesthetic effect and repeating experiments many times as necessary during the protocol.




    • Telemetry:

    Telemetry allows measuring parameters such as systolic and diastolic pressure or heart rate on awake, mobile animals in their cages through a lead implanted subcutaneously. This technology allows evaluating several physiological signals without disturbing the animal and over a period of a few days to some months.



    Flow meter (Transonnic Emka): This is the method of reference forblood flow measurement on anesthetized animal.



    Ex vivo experiments :

     A group of six pressure-arteriographs and five four-channel wire myographs is dedicated to the in vitro study of endothelial and muscular functions in isolated arteries. This facility is open to all members of the laboratory and to other laboratory in France and abroad. Vascular reactivity is investigated after in vivo measurement of the main cardiovascular parameters (blood pressure using tail cuff or telemetry, local blood flow using Transonic probes). Vascular reactivity is performed on vascular samples (from aorta to resistance arteries 100µm wide).


    • Pressure myography:

    • Flow mediated dilation
    • Myogenic tone
    • Remodeling parameters


    • Four channel wire myograph :

    Wire Myograph Systems are used to measure force in small rings of muscle tissue. The smallest possible diameter is about 60 microns :

    •  Vascular smooth muscle function
    • Vascular endothelium function
    • Length-tension relationships
    • Wall tension & morphometric measurements
    • Assessment of pharmacological reactivity  and electric stimulation






    • Organ bath :

    Pressure-flow relationship  and assessment of pharmacology on isolated and perfused Kidney and on isolated and perfused mesenteric bed.





    Industrial partnerships

    Publications involving CARFI  technology:


    • INSERM, Université de Bordeaux : Lhomme A, Gilbert G, Pele T, Deweirdt J, Henrion D, Baudrimont I, Campagnac M, Marthan R, Guibert C, Ducret T, Savineau JP, Quignard JF. Stretch-activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries. Am J Respir Cell Mol Biol. 2019 Jun;60(6):650-658.
    • CNRS, Université de Lorraine: Meyer M, Foulquier S, Dupuis F, Flament S, Grimaud L, Henrion D, Lartaud I, Monard G, Grillier-Vuissoz I, Boisbrun M. Synthesis and evaluation of new designed multiple ligands directed towards both peroxisome proliferator-activated receptor-γ and angiotensin II type 1 receptor. Eur J Med Chem. 2018 Aug 31;158:334-352.


    • INRA, Angers : Schinkovitz A, Le Pogam P, Derbré S, Vessieres E, Blanchard P, Thirumaran SL, Breard D, Aumond MC, Zehl M, Urban E, Kaur A, Jäger N, Hofer S, Kopp B, Stuppner H, Baglin I, Seraphin D, Tomasi S, Henrion D, Boustie J, Richomme P. Secondary metabolites from lichen as potent inhibitors of advanced glycation end products and vasodilative agents. Fitoterapia. 2018 Oct 16. pii: S0367-326X(18)31363-7.
    • CHU, Angers : Urbanski G, Caillon A, Poli C, Kauffenstein G, Begorre MA, Loufrani L, Henrion D, Belizna C. Hydroxychloroquine partially prevents endothelial dysfunction induced by anti-beta-2-GPI antibodies in an in vivo mouse model of antiphospholipid syndrome. PLoS One. 2018; 13(11):e0206814.
    • SCRIPPS Institute, San Diego, Californie, USA: Xu J, Mathur J, Vessières V, Hammack S, Nonomura K, Favre J, Grimaud L, Petrus M, Francisco A, Li J, Lee V, Xiang FL, Mainquist JK, Cahalan SM, Orth AP, Walker JR, Ma S, Lukacs V, Bandell M, Bordone L, Laffitte B, Xu Y, Chien S, Henrion D and Patapoutian A. GPR68 is a sensor of shear stress in endothelial cells of small-diameter arteries and regulates flow-mediated dilation and remodeling. Cell 2018;173(3):762-775.
    • CHU, Angers : Rineau E, Gaillard T, Gueguen N, Procaccio V, Henrion D, Prunier F, Lasocki S. Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model. Int J Cardiol. 2018;266:206-212
    • INSERM, PARCC, Paris : Merkulova-Rainon T, Mantsounga CS, Broquères-You D, Pinto C, Vilar J, Cifuentes D, Bonnin P, Kubis N, Henrion D, Silvestre JS, Lévy BI. Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease. Angiogenesis. 2018. doi: 10.1007/s10456-018-9608-7
    • INSERM, Université de Toulouse : Chenu C, Adlanmerini M, Boudou F, Chantalat E, Guihot AL, Toutain C, Raymond-Letron I, Vicendo P, Gadeau AP, Henrion D, Arnal JF, Lenfant F. Testosterone Prevents Cutaneous Ischemia and Necrosis in Males Through Complementary Estrogenic and Androgenic Actions. Arterioscler Thromb Vasc Biol. 2017 Mar 30.
    • INSERM, Institut des Cordeliers, Paris : Tarjus A, Maase M, Jeggle P, Martinez-Martinez E, Fassot C, Loufrani L, Henrion D, Hansen PBL, Kusche-Vihrog K, Jaisser F. The endothelial αENaC contributes to vascular endothelial function in vivo. PLoS One. 2017;12(9):e0185319.
    • Unisersité de Saint-Jacques de Compostelle, Espagne : Valenzuela R, Costa-Besada MA, Iglesias-Gonzalez J, Perez-Costas E, Villar-Cheda B, Garrido-Gil P, Melendez-Ferro M, Soto-Otero R, Lanciego JL, Henrion D, Franco R, Labandeira-Garcia JL. Mitochondrial angiotensin receptors in dopaminergic neurons. Role in cell protection and aging-related vulnerability to neurodegeneration. Cell Death Dis. 2016;7(10):e2427.
    • Ecole Vétérinaire (ONIRIS), Nantes : Montaudon E, Dubreil L, Lalanne V, Jagu B, Toumaniantz G, Thorin C, Henrion D, Desfontis JC, Martignat L, Mallem MY. Effects of long-term active immunization with the second extracellular loop of human β1- or β3-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats. Vascul Pharmacol. 2016. pii: S1537-1891(16)30159-8.
    • CNRS, Sophia-Antipolis, Nice : Retailleau K, Arhatte M, Demolombe S, Peyronnet R, Baudrie V, Jodar M, Bourreau J, Henrion D, Offermanns S, Nakamura F, Feng Y, Patel A, Duprat F, Honoré E. Arterial Myogenic Activation through Smooth Muscle Filamin A. Cell Rep. 2016;14:2050-8.
    • INSERM, Unisersité Paris V : Bedarida T, Baron S, Vibert F, Ayer A, Henrion D, Thioulouse E, Marchiol C, Beaudeux JL, Cottart CH, Nivet-Antoine V. Resveratrol Decreases TXNIP mRNA and Protein Nuclear Expressions With an Arterial Function Improvement in Old Mice. J Gerontol A Biol Sci Med Sci. 2015 Jun 3. pii: glv071.
    • CRCINA, Nantes-Angers : Marion E, Song OR, Christophe T, Babonneau J, Fenistein D, Eyer J, Letournel F, Henrion D, Clere N, Paille V, Guérineau NC, Saint André JP, Gersbach P, Altmann KH, Stinear TP, Comoglio Y, Sandoz G, Preisser L, Delneste Y, Yeramian E, Marsollier L, Brodin P. Mycobacterial toxin induces analgesia in buruli ulcer by targeting the Angiotensin pathways. Cell. 2014;157:1565-76.
    • INSERM, Toulouse: Abot A, Fontaine C, Buscato M, Solinhac R, Flouriot G, Fabre A, Drougard A, Rajan S, Laine M, Milon A, Muller I, Henrion D, Adlanmerini M, Valera MC, Gompel A, Gerard C, Pequeux C, Mestdagt M, Raymond-Letron I, Knauf C, Ferriere F, Valet P, Gourdy P, Katzenellenbogen BS, Katzenellenbogen JA, Lenfant F, Greene GL, Foidart JM, and Arnal JF. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation. EMBO Mol Med, 2014.
    • INSERM, Toulouse: Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, Liere P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, and Lenfant F. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A 111: E283-290, 2014.
    • Paris V University: Baron S, Bedarida T, Cottart CH, Vibert F, Vessieres E, Ayer A, Henrion D, Hommeril B, Paul JL, Renault G, Saubamea B, Beaudeux JL, Procaccio V, and Nivet-Antoine V. Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice. J Gerontol A Biol Sci Med Sci 69: 260-269, 2014.
    • Paris V University: Bedarida T, Baron S, Vessieres E, Vibert F, Ayer A, Marchiol-Fournigault C, Henrion D, Paul JL, Noble F, Golmard JL, Beaudeux JL, Cottart CH, and Nivet-Antoine V. High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age. Am J Physiol Heart Circ Physiol 307: H649-657, 2014.
    • INSERM, Toulouse: Adlanmerini M, Solinhac R, Abot A, Fabre A, Raymond-Letron I, Guihot AL, Boudou F, Sautier L, Vessieres E, Kim SH, Liere P, Fontaine C, Krust A, Chambon P, Katzenellenbogen JA, Gourdy P, Shaul PW, Henrion D, Arnal JF, and Lenfant F. Mutation of the palmitoylation site of estrogen receptor alpha in vivo reveals tissue-specific roles for membrane versus nuclear actions. Proc Natl Acad Sci U S A 111: E283-E290, 2013
    • College de France, INSERM, Paris : Bouleti C, Mathivet T, Coqueran B, Serfaty JM, Lesage M, Berland E, Ardidie-Robouant C, Kauffenstein G, Henrion D, Lapergue B, Mazighi M, Duyckaerts C, Thurston G, Valenzuela DM, Murphy AJ, Yancopoulos GD, Monnot C, Margaill I, and Germain S. Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke. Eur Heart J 34: 3657-3668, 2013
    • Charité University, Berlin : Cristofaro B, Shi Y, Faria M, Suchting S, Leroyer AS, Trindade A, Duarte A, Zovein AC, Iruela-Arispe ML, Nih LR, Kubis N, Henrion D, Loufrani L, Todiras M, Schleifenbaum J, Gollasch M, Zhuang ZW, Simons M, Eichmann A, and le Noble F. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models. Development 140: 1720-1729, 2013.
    • PARCC INSERM, Paris: Bergaya S, Faure S, Baudrie V, Rio M, Escoubet B, Bonnin P, Henrion D, Loirand G, Achard JM, Jeunemaitre X, and Hadchouel J. WNK1 regulates vasoconstriction and blood pressure response to alpha 1-adrenergic stimulation in mice. Hypertension 58: 439-445, 2011.
    • INSERM (CRCNA, Nantes-Angers) : Clere N, Corre I, Faure S, Guihot AL, Vessières E, Chalopin M, Morel A, Coqueret O, Hein L, Delneste Y, Paris F, Henrion D. Deficiency or blockade of angiotensin II type 2 receptor delays tumorigenesis by inhibiting malignant cell proliferation and angiogenesis. Int J Cancer, 2010
    • PaVé (INRA, Angers): Duge de Bernonville T, Guyot S, Paulin JP, Gaucher M, Loufrani L, Henrion D, Derbre S, Guilet D, Richomme P, Dat JF, Brisset MN. Dihydrochalcones: Implication in resistance to oxidative stress and bioactivities against advanced glycation end-products and vasoconstriction. Phytochemistry. 2010;71:443-52.
    • INSERM, Nantes : Guilluy C, Bregeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nature Medicine. 2010;16(2):183-90.
    • Berlin, « Charité » Hospital : Buschmann I, Pries A, Styp-Rekowska B, Hillmeister P, Shi Y, Duelsner A, Hoefer I, Gatzke N, Wang H, Lehmann K, Henrion D, Loufrani L, Hlushchuk R, Djonov V, le Noble F. Pulsatile shear and Gja5 (Connexin-40) modulate arterial identity and remodeling events during flow driven arteriogenesis. Development, 2010 ;137:2187-96.
    • Université de Paris VI- INSERM : Nguyen Dinh Cat A, Griol-Charhbili V, Loufrani L, Labat C, Benjamin L, Farman N, Lacolley P, Henrion D, Jaisser F. The endothelial mineralocorticoid receptor regulates vasoconstrictor tone and blood pressure. FASEB J. 2010;24:2454-63
    • Monash University, Melbourne, Australia: Koïtka A, Cao Z, Koh P, Watson AM, Sourris KC, Loufrani L, Soro-Paavonen A, Walther T, Woollard KJ, Jandeleit-Dahm KA, Cooper ME, Allen TJ. Angiotensin II subtype 2 receptor blockade and deficiency attenuate the development of atherosclerosis in an apolipoprotein E-deficient mouse model of diabetes. Diabetologia. 2010;53:584-92
    • Université de Lübeck : Lund N, Henrion D, Tiede P, Ziche M, Schunkert H, Ito WD. Vimentin expression influences flow dependent VASP phosphorylation and regulates cell migration and proliferation. Biochem Biophys Res Commun. 2010;395:401-6.
    • INSERM, Nancy ; CHU d’Angers: Sennoun N, Baron-Menguy C, Burban M, Lecompte T, Andriantsitohaina R, Henrion D, Mercat A, Asfar P, Levy B, Meziani F. Recombinant human activated protein C improves endotoxemia-induced endothelial dysfunction: A blood free model in isolated mouse arteries. Am J Physiol. 2009, 2009;297:H277-282.
    • CNRS – Sofia-Antipolis: Sharif-Naeini R, Folgering JH, Bichet D, Duprat F, Lauritzen I, Arhatte M, Jodar M, Dedman A, Chatelain FC, Schulte U, Retailleau K, Loufrani L, Patel A, Sachs F, Delmas P, Peters DJ, Honoré E. Polycystin-1 and -2 dosage regulates pressure sensing. Cell. 2009 30;139:587-96
    • Université de New-York (Valhalla, USA) : Rutkai I, Feher A, Erdei N, Henrion D, Papp Z, Edes I, Koller A, Kaley G, Bagi Z. Activation of prostaglandin E2 EP1 receptor increases arteriolar tone and blood pressure in mice with type 2 diabetes. Cardiovasc Res. 2009;83:148-154.
    • Ecole Vétérinaire, Nantes : Delphine Holopherne, Mohamed Yassine Mallem, Eric Belin de Chantemele, Marc Gogny, Daniel Henrion, Jacques Noireaud, Jean-Claude Desfontis. CGP12177-induced hAemodynamic and vascular effects in normotensive and hypertensive rats. Europ. J. Pharmacol. 2008, 591:196-202
    • INSERM, Paris : Loufrani L, Retailleau K, Bocquet A, Dumont O, Danker K, Louis H, Lacolley P, Henrion D. Key role of the {alpha}1-{beta}1 integrin in the activation of PI3Kinase-Akt by flow (shear stress) in resistance arteries. Am J Physiol Heart Circ Physiol. 2008;294:H1906-13
    • INSERM, Nantes: Guilluy C, Rolli-Derkinderen M, Loufrani L, Bourgé A, Henrion D, Sabourin L, Loirand G, Pacaud P. Ste20-related kinase SLK phosphorylates Ser 188 of RhoA to induce vasodilation in response to Angiotensin II type 2 receptor activation. Circ. Res. 2008;102:1265-74.
    • INSERM, Paris : E. Belin de Chantemèle, F. Pinaud, A Bocquet, V. Domenga, L Loufrani, A. Joutel, D. Henrion. Notch3 receptors involvement in the control of vascular mechanotransduction. Arterioscler Thromb Vasc Biol. 2008;28:2216-24.
    • CNRS, Nice: Garry A, Fromy B, Blondeau N, Henrion D, Braud F, Gounon P, Guy N, Heurtaux C, Lazdunski M, Saumet JL. Altered acetylcholine and bradykinin and cutaneous pressure-induced vasodilation in mice lacking the TREK-1 potassium channel – The endothelial link. EMBO Rep. 2007 ; 8:354-9.
    • INSERM, Paris : Chansel D, Ciroldi M, Vandermeersch S, Jackson LF, Gomez AM, Henrion D, Lee DC, Coffman TM, Richard S, Dussaule JC, Tharaux PL.Heparin binding EGF is necessary for vasospastic response to endothelin. FASEB J. 2006;20:1936-8 ;
    • INSERM, Nancy: Mercier N, Osborne-Pellegrin M, El Hadri K, Kakou A, Labat C, Loufrani L, Henrion D, Challande P, Jalkanen S, Feve B, Lacolley P. Carotid arterial stiffness, elastic fibre network and vasoreactivity in semicarbazide-sensitive amine-oxidase null mouse. Cardiovasc Res. 2006;72:349-57.


    Postal address

    MITOVASCUMR CNRS 6015 - INSERM U1083Bâtiment IRIS 2 3 rue Roger Amsler49100 ANGERSFRANCEPhone : +33244688260Fax : +33244688261


    daniel.henrion @ univ-angers.fr


    Daniel Henrion : +33244688275
    Emilie Vessières : +33244688267