Jonathan H Soslow1, Meng Xu2, James C Slaughter2, Kimberly Crum3, Joshua D Chew3, W Bryan Burnette4, Yan Ru Su5, Kelsey Tomasek5, David A Parra3, Larry W Markham6. 1. Thomas P Graham Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: jonathan.h.soslow@vumc.org. 2. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee. 3. Thomas P Graham Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. 4. Division of Neurology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee. 5. Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 6. Thomas P Graham Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Abstract
BACKGROUND: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy. METHODS AND RESULTS: Prospectively enrolled DMD subjects (n = 42) underwent cardiac magnetic resonance imaging for function and late gadolinium enhancement (LGE), including LGE severity from 0 (no LGE) to 4 (severe). Serum from DMD and healthy male control subjects (n = 15) analyzed for MMPs 1, 2, 3, 7, 9, and 10 and TIMPs 1-4. MMP1, MMP7, and MMP10 were higher in DMD than in control (respectively, median 5080 pg/mL vs 2120 pg/mL [P = .007], 2170 pg/mL vs 1420 pg/mL [P < .001], and 216 pg/mL vs 140pg/mL [P = .040]); TIMP4 was lower in DMD (124 pg/mL vs 263 pg/mL; P = .046). Within DMD, MMP7 correlated inversely with left ventricular ejection fraction (r = -0.40; P = .012) and directly with strain (r = 0.54; P = .001) and LGE severity (r = 0.47; P = .003). MMP7 was higher in DMD patients with LGE compared with those without LGE and control subjects (P < .001). CONCLUSIONS: Multiple MMPs are elevated in DMD compared with control subjects. MMP7 is related to DMD cardiac dysfunction and myocardial fibrosis, possibly through remodeling of the extracellular matrix.
BACKGROUND:Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy. METHODS AND RESULTS: Prospectively enrolled DMD subjects (n = 42) underwent cardiac magnetic resonance imaging for function and late gadolinium enhancement (LGE), including LGE severity from 0 (no LGE) to 4 (severe). Serum from DMD and healthy male control subjects (n = 15) analyzed for MMPs 1, 2, 3, 7, 9, and 10 and TIMPs 1-4. MMP1, MMP7, and MMP10 were higher in DMD than in control (respectively, median 5080 pg/mL vs 2120 pg/mL [P = .007], 2170 pg/mL vs 1420 pg/mL [P < .001], and 216 pg/mL vs 140pg/mL [P = .040]); TIMP4 was lower in DMD (124 pg/mL vs 263 pg/mL; P = .046). Within DMD, MMP7 correlated inversely with left ventricular ejection fraction (r = -0.40; P = .012) and directly with strain (r = 0.54; P = .001) and LGE severity (r = 0.47; P = .003). MMP7 was higher in DMDpatients with LGE compared with those without LGE and control subjects (P < .001). CONCLUSIONS: Multiple MMPs are elevated in DMD compared with control subjects. MMP7 is related to DMD cardiac dysfunction and myocardial fibrosis, possibly through remodeling of the extracellular matrix.
Authors: Scott A Simpson; Suzanne L Field; Meng Xu; Benjamin R Saville; David A Parra; Jonathan H Soslow Journal: Pediatr Cardiol Date: 2017-12-14 Impact factor: 1.655
Authors: Subha V Raman; Kan N Hor; Wojciech Mazur; Nancy J Halnon; John T Kissel; Xin He; Tam Tran; Suzanne Smart; Beth McCarthy; Michael D Taylor; John L Jefferies; Jill A Rafael-Fortney; Jeovanna Lowe; Sharon L Roble; Linda H Cripe Journal: Lancet Neurol Date: 2014-12-30 Impact factor: 44.182
Authors: Andrew D Posner; Jonathan H Soslow; W Bryan Burnette; Aihua Bian; Ayumi Shintani; Douglas B Sawyer; Larry W Markham Journal: J Neuromuscul Dis Date: 2016-03-03
Authors: David M Connuck; Lynn A Sleeper; Steven D Colan; Gerald F Cox; Jeffrey A Towbin; April M Lowe; James D Wilkinson; E John Orav; Leigha Cuniberti; Bonnie A Salbert; Steven E Lipshultz Journal: Am Heart J Date: 2008-03-19 Impact factor: 4.749
Authors: Mary Killian; Maciej S Buchowski; Thomas Donnelly; W Bryan Burnette; Larry W Markham; James C Slaughter; Meng Xu; Kimberly Crum; Bruce M Damon; Jonathan H Soslow Journal: Neuromuscul Disord Date: 2020-02-20 Impact factor: 4.296
Authors: Larry W Markham; Jonathan H Soslow; Aryaz Sheybani; Kim Crum; Frank J Raucci; William B Burnette Journal: Pediatr Res Date: 2021-08-24 Impact factor: 3.756
Authors: Christopher F Spurney; Deborah Ascheim; Lawrence Charnas; Linda Cripe; Kan Hor; Nicholas King; Kathi Kinnett; Elizabeth M McNally; John-Michael Sauer; Lee Sweeney; Chet Villa; Larry W Markham Journal: Open Heart Date: 2021-03
Authors: Frank J Raucci; Meng Xu; Kristen George-Durrett; Kimberly Crum; James C Slaughter; David A Parra; Larry W Markham; Jonathan H Soslow Journal: J Cardiovasc Magn Reson Date: 2021-04-29 Impact factor: 5.364