title: GDF11 does not rescue aging-related pathological hypertrophy.
abstract: BACKGROUND
  Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH) and restoring GDF11 to normal levels in old mice rescued PCH.
  
  
  OBJECTIVE
  To determine whether and by what mechanism GDF11 rescues aging dependent PCH.
  
  
  RESULTS
  Twenty-four-month-old C57BL/6 mice were given a daily injection of either recombinant (r) GDF11 at 0.1 mg/kg or vehicle for 28 days. rGDF11 bioactivity was confirmed in vitro. After treatment, rGDF11 levels were significantly increased, but there was no significant effect on either heart weight or body weight. Heart weight/body weight ratios of old mice were not different from 8- or 12-week-old animals, and the PCH marker atrial natriuretic peptide was not different in young versus old mice. Ejection fraction, internal ventricular dimension, and septal wall thickness were not significantly different between rGDF11 and vehicle-treated animals at baseline and remained unchanged at 1, 2, and 4 weeks of treatment. There was no difference in myocyte cross-sectional area rGDF11 versus vehicle-treated old animals. In vitro studies using phenylephrine-treated neonatal rat ventricular myocytes, to explore the putative antihypertrophic effects of GDF11, showed that GDF11 did not reduce neonatal rat ventricular myocytes hypertrophy, but instead induced hypertrophy.
  
  
  CONCLUSIONS
  Our studies show that there is no age-related PCH in disease-free 24-month-old C57BL/6 mice and that restoring GDF11 in old mice has no effect on cardiac structure or function.
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Shavonn C
authors.initials: SC
authors.lastname: Smith
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Polina
authors.initials: P
authors.lastname: Gross
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Timothy
authors.initials: T
authors.lastname: Starosta
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Sadia
authors.initials: S
authors.lastname: Mohsin
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Michael
authors.initials: M
authors.lastname: Franti
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Priyanka
authors.initials: P
authors.lastname: Gupta
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: David
authors.initials: D
authors.lastname: Hayes
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Maria
authors.initials: M
authors.lastname: Myzithras
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Julius
authors.initials: J
authors.lastname: Kahn
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: James
authors.initials: J
authors.lastname: Tanner
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Steven M
authors.initials: SM
authors.lastname: Weldon
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Ashraf
authors.initials: A
authors.lastname: Khalil
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Xinji
authors.initials: X
authors.lastname: Guo
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Abdelkarim
authors.initials: A
authors.lastname: Sabri
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell).
authors.forename: Scott
authors.initials: S
authors.lastname: MacDonnell
authors.affiliation: From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA (S.C.S., Xiaoxiao Zhang, Xiaoying Zhang, P.G., T.S., S Mohsin, X.G., A.S., X.C., S.R.H.); and Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (M.F., P.G., D.H., M.M., J.K., J.T., S.M.W., A.K., S. MacDonnell). srhouser@temple.edu.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Houser
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D055412:Growth Differentiation Factors / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D019485:Bone Morphogenetic Proteins; C492266:GDF11 protein, human; D055412:Growth Differentiation Factors; D011994:Recombinant Proteins
keywords: aging; body weight; cardiac function tests; growth differentiation factors; transforming growth factor beta