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Barallobre-Barreiro J, Radovits T, Fava M, et al. Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling. Circulation. 2021;144(25):2021-2034doi: 10.1161/CIRCULATIONAHA.121.055732.
Barallobre-Barreiro, J., Radovits, T., Fava, M., Mayr, U., Lin, W. Y., Ermolaeva, E., Martínez-López, D., Lindberg, E. L., Duregotti, E., Daróczi, L., Hasman, M., Schmidt, L. E., Singh, B., Lu, R., Baig, F., Siedlar, A. M., Cuello, F., Catibog, N., Theofilatos, K., Shah, A. M., Crespo-Leiro, M. G., Doménech, N., Hübner, N., Merkely, B., & Mayr, M. (2021). Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling. Circulation, 144(25), 2021-2034. https://doi.org/10.1161/CIRCULATIONAHA.121.055732
Barallobre-Barreiro, Javier, et al. "Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling." Circulation vol. 144,25 (2021): 2021-2034. doi: https://doi.org/10.1161/CIRCULATIONAHA.121.055732
Barallobre-Barreiro J, Radovits T, Fava M, Mayr U, Lin WY, Ermolaeva E, Martínez-López D, Lindberg EL, Duregotti E, Daróczi L, Hasman M, Schmidt LE, Singh B, Lu R, Baig F, Siedlar AM, Cuello F, Catibog N, Theofilatos K, Shah AM, Crespo-Leiro MG, Doménech N, Hübner N, Merkely B, Mayr M. Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling. Circulation. 2021 Dec 21;144(25):2021-2034. doi: 10.1161/CIRCULATIONAHA.121.055732. Epub 2021 Nov 22. PMID: 34806902; PMCID: PMC8687617.
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Circulation. 2021 Dec 21;144(25):2021-2034. doi: 10.1161/CIRCULATIONAHA.121.055732. Epub 2021 Nov 22.

Extracellular Matrix in Heart Failure: Role of ADAMTS5 in Proteoglycan Remodeling.

Circulation

Javier Barallobre-Barreiro, Tamás Radovits, Marika Fava, Ursula Mayr, Wen-Yu Lin, Elizaveta Ermolaeva, Diego Martínez-López, Eric L Lindberg, Elisa Duregotti, László Daróczi, Maria Hasman, Lukas E Schmidt, Bhawana Singh, Ruifang Lu, Ferheen Baig, Aleksandra Malgorzata Siedlar, Friederike Cuello, Norman Catibog, Konstantinos Theofilatos, Ajay M Shah, Maria G Crespo-Leiro, Nieves Doménech, Norbert Hübner, Béla Merkely, Manuel Mayr

Affiliations

  1. King's BHF Centre of Research Excellence, London, UK (J.B.-B., M.F., U.M., W.-Y.L., E.E., E.D., M.H., L.E.S., B.S., R.L., F.B., A.M.S., N.C., K.T., A.M.S., M.M.).
  2. Heart and Vascular Center, Department of Cardiology, Semmelweis University, Budapest, Hungary (T.R., L.D., B.M.).
  3. Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (W.-Y.L.).
  4. IIS-Fundación Jiménez Díaz-Universidad Autónoma and CIBERCV, Madrid, Spain (D.M.-L.).
  5. Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany (E.L.L., N.H.).
  6. Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, German Center for Heart Research (DZHK), Hamburg, Germany (F.C.).
  7. Instituto de Investigación Biomédica de A Coruña (INIBIC)-CIBERCV, Complexo Hospitalario Universitario de A Coruña (CHUAC), Universidade da Coruña, Spain (M.G.C.-L., N.D.).
  8. Charité-Universitätsmedizin, Berlin, Germany (N.H.).
  9. DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany (N.H.).

PMID: 34806902 PMCID: PMC8687617 DOI: 10.1161/CIRCULATIONAHA.121.055732

Abstract

BACKGROUND: Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown.

METHODS: Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5

RESULTS: Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5

CONCLUSIONS: Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that β-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content.

Keywords: adrenergic beta-agonists; extracellular matrix; heart failure; proteoglycans

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