Local production of tenascin-C acts as a trigger for monocyte/macrophage recruitment that provokes cardiac dysfunction

Autor: Anne-Catherine Prats, Dounia Abbadi, Marianne Dutaur, Florence Tortosa, Danièle Daviaud, Jerome Roncalli, Denis Calise, Edith Renaud-Gabardos, Frédérique Gaits-Iacovoni, Christine Delage, Joffrey Pozzo, Mathilde Bizou, Angelo Parini, Nathalie Pizzinat, Victorine Douin-Echinard, Fanny Laroumanie
Přispěvatelé: Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2017
Předmět:
Male
rho GTP-Binding Proteins
0301 basic medicine
RHOA
Physiology
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Monocytes
Ventricular Function
Left
Ventricular Dysfunction
Left
Cell Movement
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Macrophage
ComputingMilieux_MISCELLANEOUS
Mice
Knockout
rho-Associated Kinases
Ventricular Remodeling
biology
Chemistry
Tenascin C
Tenascin
[SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular Networks [q-bio.MN]
musculoskeletal system
Cell biology
Haematopoiesis
Phenotype
medicine.anatomical_structure
Cellular Microenvironment
Hypertrophy
Left Ventricular
Chemokines
Inflammation Mediators
medicine.symptom
Cardiology and Cardiovascular Medicine
Signal Transduction
Macrophage polarization
Inflammation
03 medical and health sciences
Physiology (medical)
medicine
Animals
Pressure overload
Macrophages
Myocardium
Monocyte
Fibrosis
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Immunology
biology.protein
rhoA GTP-Binding Protein
Zdroj: Cardiovascular Research
Cardiovascular Research, Oxford University Press (OUP), 2018, 114 (1), pp.123-137. ⟨10.1093/cvr/cvx221⟩
ISSN: 1755-3245
0008-6363
DOI: 10.1093/cvr/cvx221
Popis: Aims Tenascin-C (TNC) is an endogenous danger signal molecule strongly associated with inflammatory diseases and with poor outcome in patients with cardiomyopathies. Its function within pathological cardiac tissue during pressure overload remains poorly understood. Methods and results We showed that TNC accumulates after 1 week of transverse aortic constriction (TAC) in the heart of 12-week-old male mice. By cross bone marrow transplantation experiments, we determined that TNC deposition relied on cardiac cells and not on haematopoietic cells. The expression of TNC induced by TAC, or by administration of a recombinant lentivector coding for TNC, triggered a pro-inflammatory cardiac microenvironment, monocyte/macrophage (MO/MΦ) accumulation, and systolic dysfunction. TNC modified macrophage polarization towards the pro-inflammatory phenotype and stimulated RhoA/Rho-associated protein kinase (ROCK) pathways to promote mesenchymal to amoeboid transition that enhanced macrophage migration into fibrillar collagen matrices. The amplification of inflammation and MO/MΦ recruitment by TNC was abrogated by genetic invalidation of TNC in knockout mice. These mice showed less ventricular remodelling and an improved cardiac function after TAC as compared with wild-type mice. Conclusions By promoting a pro-inflammatory microenvironment and macrophage migration, TNC appears to be a key factor to enable the MO/MΦ accumulation within fibrotic hearts leading to cardiac dysfunction. As TNC is highly expressed during inflammation and sparsely during the steady state, its inhibition could be a promising therapeutic strategy to control inflammation and immune cell infiltration in heart disease.
Databáze: OpenAIRE
Externí odkaz: