The fibroblast hormone Endotrophin is a biomarker of mortality in chronic diseases
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The fibroblast hormone Endotrophin is a biomarker of mortality in chronic diseases. / Genovese, Federica; Bager, Cecilie; Frederiksen, Peder; Vazquez, Dario; Sand, Jannie Marie Bülow; Jenkins, R. Gisli; Maher, Toby M.; Stewart, Iain D.; Molyneaux, Philip L.; Fahy, William A.; Wain, Louise V.; Vestbo, Jørgen; Nanthakumar, Carmel; Shaker, Saher Burhan; Hoyer, Nils; Leeming, Diana Julie; George, Jacob; Trebicka, Jonel; Rasmussen, Daniel Guldager Kring; Hansen, Michael K.; Cockwell, Paul; Kremer, Daan; Bakker, Stephan JL; Selby, Nicholas M.; Reese-Petersen, Alexander Lynge; González, Arantxa; Núñez, Julio; Rossing, Peter; Nissen, Neel I.; Boisen, Mogens Karsbøl; Chen, Inna M.; Zhao, Lei; Karsdal, Morten A.; Schuppan, Detlef.
I: Matrix Biology, Bind 132, 2024, s. 1-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The fibroblast hormone Endotrophin is a biomarker of mortality in chronic diseases
AU - Genovese, Federica
AU - Bager, Cecilie
AU - Frederiksen, Peder
AU - Vazquez, Dario
AU - Sand, Jannie Marie Bülow
AU - Jenkins, R. Gisli
AU - Maher, Toby M.
AU - Stewart, Iain D.
AU - Molyneaux, Philip L.
AU - Fahy, William A.
AU - Wain, Louise V.
AU - Vestbo, Jørgen
AU - Nanthakumar, Carmel
AU - Shaker, Saher Burhan
AU - Hoyer, Nils
AU - Leeming, Diana Julie
AU - George, Jacob
AU - Trebicka, Jonel
AU - Rasmussen, Daniel Guldager Kring
AU - Hansen, Michael K.
AU - Cockwell, Paul
AU - Kremer, Daan
AU - Bakker, Stephan JL
AU - Selby, Nicholas M.
AU - Reese-Petersen, Alexander Lynge
AU - González, Arantxa
AU - Núñez, Julio
AU - Rossing, Peter
AU - Nissen, Neel I.
AU - Boisen, Mogens Karsbøl
AU - Chen, Inna M.
AU - Zhao, Lei
AU - Karsdal, Morten A.
AU - Schuppan, Detlef
N1 - Publisher Copyright: © 2024
PY - 2024
Y1 - 2024
N2 - Fibrosis, driven by fibroblast activities, is an important contributor to morbidity and mortality in most chronic diseases. Endotrophin, a signaling molecule derived from processing of type VI collagen by highly activated fibroblasts, is involved in fibrotic tissue remodeling. Circulating levels of endotrophin have been associated with an increased risk of mortality in multiple chronic diseases. We conducted a systematic literature review collecting evidence from original papers published between 2012 and January 2023 that reported associations between circulating endotrophin (PRO[sbnd]C6) and mortality. Cohorts with data available to the study authors were included in an Individual Patient Data (IPD) meta-analysis that evaluated the association of PRO[sbnd]C6 with mortality (PROSPERO registration number: CRD42023340215) after adjustment for age, sex and BMI, where available. In the IPD meta-analysis including sixteen cohorts of patients with different non-communicable chronic diseases (NCCDs) (N = 15,205) the estimated summary hazard ratio for 3-years all-cause mortality was 2.10 (95 % CI 1.75—2.52) for a 2-fold increase in PRO[sbnd]C6, with some heterogeneity observed between the studies (I2=70 %). This meta-analysis is the first study documenting that fibroblast activities, as quantified by circulating endotrophin, are independently associated with mortality across a broad range of NCCDs. This indicates that, irrespective of disease, interstitial tissue remodeling, and consequently fibroblast activities, has a central role in adverse clinical outcomes, and should be considered with urgency from drug developers as a target to treat.
AB - Fibrosis, driven by fibroblast activities, is an important contributor to morbidity and mortality in most chronic diseases. Endotrophin, a signaling molecule derived from processing of type VI collagen by highly activated fibroblasts, is involved in fibrotic tissue remodeling. Circulating levels of endotrophin have been associated with an increased risk of mortality in multiple chronic diseases. We conducted a systematic literature review collecting evidence from original papers published between 2012 and January 2023 that reported associations between circulating endotrophin (PRO[sbnd]C6) and mortality. Cohorts with data available to the study authors were included in an Individual Patient Data (IPD) meta-analysis that evaluated the association of PRO[sbnd]C6 with mortality (PROSPERO registration number: CRD42023340215) after adjustment for age, sex and BMI, where available. In the IPD meta-analysis including sixteen cohorts of patients with different non-communicable chronic diseases (NCCDs) (N = 15,205) the estimated summary hazard ratio for 3-years all-cause mortality was 2.10 (95 % CI 1.75—2.52) for a 2-fold increase in PRO[sbnd]C6, with some heterogeneity observed between the studies (I2=70 %). This meta-analysis is the first study documenting that fibroblast activities, as quantified by circulating endotrophin, are independently associated with mortality across a broad range of NCCDs. This indicates that, irrespective of disease, interstitial tissue remodeling, and consequently fibroblast activities, has a central role in adverse clinical outcomes, and should be considered with urgency from drug developers as a target to treat.
KW - Biomarker
KW - Endotrophin
KW - Fibroblast activity
KW - Mortality
KW - NCCDs
KW - PRO-C6
KW - Type VI collagen
U2 - 10.1016/j.matbio.2024.06.003
DO - 10.1016/j.matbio.2024.06.003
M3 - Journal article
C2 - 38871093
AN - SCOPUS:85196173293
VL - 132
SP - 1
EP - 9
JO - Matrix Biology
JF - Matrix Biology
SN - 0945-053X
ER -
ID: 395869761