Gremlin-1 Identifies Fibrosis and Predicts Adverse Outcome in Patients With Heart Failure Undergoing Endomyocardial Biopsy

Mueller, Karin; Tavlaki, Elli; Schneider, Martina; Jorbenadze, Rezo; Geisler, Tobias; Kandolf, Reinhard; Gawaz, Meinrad; Zuern, Christine S.; Mueller, Iris

doi:10.1016/j.cardfail.2013.09.001

Cited by 31 publications

(34 citation statements)

References 33 publications

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“…Gremlin-1 has been found to predict adverse outcome in heart failure, is highly correlated to myocardial fibrosis grade (26), and was initially identified as being induced under rather high glucose conditions (27). Interestingly Gremlin has been found to be overexpressed in idiopathic pulmonary fibrosis (28), a devastating disease.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 (IL-6) Trans Signaling Drives a STAT3-dependent Pathway That Leads to Hyperactive Transforming Growth Factor-β (TGF-β) Signaling Promoting SMAD3 Activation and Fibrosis via Gremlin Protein

O’Reilly

Ciechomska

Cant

et al. 2014

Journal of Biological Chemistry

214

168

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 (IL-6) Trans Signaling Drives a STAT3-dependent Pathway That Leads to Hyperactive Transforming Growth Factor-β (TGF-β) Signaling Promoting SMAD3 Activation and Fibrosis via Gremlin Protein

O’Reilly

Ciechomska

Cant

et al. 2014

Journal of Biological Chemistry

214

168

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“…In a recent large outcome-based study, high expression of Gremlin-1 on endomyocardial biopsy was found to predict poor outcome in patients with heart failure [35]. In this study, endomyocardial biopsies from 214 patients with nonischemic congestive heart failure were assessed for Gremlin-1 expression (Fig.…”

Section: Germlin-1 As a Novel Prognostic Marker In Congestive Heart Fmentioning

confidence: 99%

Novel prognostic tissue markers in congestive heart failure

Stone

2015

Cardiovascular Pathology

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“…Gremlins have been shown to be involved not only in embryonic development, but also in brogenesis in the lung, heart, kidney, and liver [16][17][18][19] . For example, Grem1 is highly expressed in the lungs of patients with IPF, in which TGF secretion and SMA expression are higher than in healthy adult lung broblasts 17 .…”

Section: Discussionmentioning

confidence: 99%

“…Grem1 / mice exhibit germline lethality, whereas in Grem1 / mice the bone is not fully developed, resulting in severe developmental defects compared with wild-type mice 15 . In addition, Grem1 is highly expressed in idiopathic pulmonary brosis IPF , diabetic nephropathy, and brotic processes in the liver and heart [16][17][18][19] .…”

mentioning

confidence: 99%

Role of Gremlins in the Aortic Arch of Spontaneously Hypertensive and Hyperlipidemic Rats

Kawaguchi

Iwai

Miyazawa

et al. 2016

Showa Univ J Med Sci

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: Atherosclerosis is a lifestyle-related disease that plays a major role in cardiovascular disease. Recently, we found that gene expression of Gremlin 2, an antagonist of bone morphogenetic protein BMP , was signi cantly increased in the aorta of spontaneously hypertensive and hyperlipidemic rats SHHRs fed a highfat, 30 sucrose solution diet HFDS . However, the role of Gremlin 1 Grem1 and Gremlin 2 Grem2 in the aortic arch of rats under hypertensive, hyperlipidemic, and hyperglycemic conditions remains unclear. Therefore, in the present study we investigated the molecular role of Gremlins in the aorta of SHHRs. Four-month-old male Sprague-Dawley rats and SHHRs were fed a normal diet or the HFDS ad libitum for 4 months. Then, gene and protein expression was analyzed using quantitative polymerase chain reaction and western blotting, respectively. Grem1 and Grem2 protein expression was increased, whereas phosphorylated Smad1/5 protein expression was low, in the aorta of SHHRs fed the HFDS. In addition, the expression of the downstream gene targets of BMP, namely inhibitor of DNA binding 1 Id1 and atonal homolog 8 Atoh8 , was decreased in aortas of SHHRs fed the HFDS. Furthermore, mRNA expression of Snail, -smooth muscle actin SMA , and Fibronectin was increased in SHHRs fed the HFDS. These ndings suggest that upregulation of Gremlins attenuates the activation of BMP signaling, which contributes to brogenesis of the aorta.

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Gremlin-1 Identifies Fibrosis and Predicts Adverse Outcome in Patients With Heart Failure Undergoing Endomyocardial Biopsy

Cited by 31 publications

References 33 publications

Interleukin-6 (IL-6) Trans Signaling Drives a STAT3-dependent Pathway That Leads to Hyperactive Transforming Growth Factor-β (TGF-β) Signaling Promoting SMAD3 Activation and Fibrosis via Gremlin Protein

Interleukin-6 (IL-6) Trans Signaling Drives a STAT3-dependent Pathway That Leads to Hyperactive Transforming Growth Factor-β (TGF-β) Signaling Promoting SMAD3 Activation and Fibrosis via Gremlin Protein

Novel prognostic tissue markers in congestive heart failure

Role of Gremlins in the Aortic Arch of Spontaneously Hypertensive and Hyperlipidemic Rats

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