المؤلفون: Thum, T., Hoeber, S., Froese, S., Klink, I., Stichtenoth, D.O., Galuppo, P., Jakob, M., Tsikas, D., Anker, S.D., Poole-Wilson, P.A., Borlak, J., Ertl, G., Bauersachs, J.

مصطلحات موضوعية: endothelial progenitor cell, aging, Insulin-like-growth-factor-1, growth hormone

الوقت: 610, 620, 616

الوصف: S.434-443 ; Aging is associated with an increased risk for atherosclerosis. A possible cause is low numbers and dysfunction of endothelial progenitor cells (EPC) which insufficiently repair damaged vascular walls. We hypothesized that decreased levels of insulin-like growth factor-1 (IGF-1) during age contribute to dysfunctional EPC. We measured the effect of growth hormone (GH), which increases endogenous IGF-1 levels, on EPC in mice and human subjects. We compared EPC number and function in healthy middle-aged male volunteers (57.4 +/- 1.4 years) before and after a 10 day treatment with recombinant GH (0.4 mg/d) with that of younger and elderly male subjects (27.5 +/- 0.9 and 74.1 +/- 0.9 years). Middle-aged and elderly subjects had lower circulating CD133 (+)/VEGFR-2(+) EPC with impaired function and increased senescence. GH treatment in middle-aged subjects elevated IGF-1 levels (126.0 +/- 7.2 ng/mL versus 241.1 +/- 13.8 ng/mL; P < 0.0001), increased circulating EPC with improved colony forming and migratory capacity, enhanced incorporation into tube-like structures, and augmented endothelial nitric oxide synthase expression in EPC comparable to that of the younger group. EPC senescence was attenuated, whereas telomerase activity was increased after GH treatment. Treatment of aged mice with GH ( 7 days) or IGF-1 increased IGF-1 and EPC levels and improved EPC function, whereas a two day GH treatment did not alter IGF-1 or EPC levels. Ex vivo treatment of EPC from elderly individuals with IGF-1 improved function and attenuated cellular senescence. IGF-1 stimulated EPC differentiation, migratory capacity and the ability to incorporate into forming vascular networks in vitro via the IGF-1 receptor. IGF-1 increased telomerase activity, endothelial nitric oxide synthase expression, phosphorylation and activity in EPC in a phosphoinositide-3-kinase/Akt dependent manner. Small interference RNA-mediated knockdown of endothelial nitric oxide synthase in EPC abolished the IGF-1 effects. Growth hormone-mediated ...

العلاقة: Circulation research. Journal of the American Heart Association; https://publica.fraunhofer.de/handle/publica/212980Test

الإتاحة: https://doi.org/10.1161/01.RES.0000257912.78915.afTest
https://publica.fraunhofer.de/handle/publica/212980Test

المؤلفون: CICOIRA, Mariantonietta, Kalra Pr, Anker S.d.

المساهمون: Cicoira, Mariantonietta, Kalra, Pr, Anker, S. d.

مصطلحات موضوعية: heart failure, treatment, growth hormone

الوصف: In recent years the administration of recombinant human growth hormone (GH) has received great attention. This review compares the potential of this therapeutic intervention in heart failure with that in other diseases where wasting is commonly seen. The pathophysiologic importance of GH and insulin-like growth factor (IGF)-I in these conditions will be discussed. METHODS AND RESULTS: Abnormalities of the GH-IGF-I axis play an important role in the development of cachexia in chronic illnesses. GH resistance is a major determinant of the wasting process, acting through several different mechanisms: increased catabolism, impaired anabolism, and enhanced apoptosis in peripheral tissues. GH therapy has been evaluated in chronic heart failure (CHF); acquired GH resistance may explain the general lack of therapeutic success in the majority of studies. The assessment of plasma levels of GH, IGF-I, and, in particular, GH binding protein may help to guide dosing of GH for CHF patients. CONCLUSIONS: GH resistance might be overcome by use of intermittent or higher doses of GH, or alternatively by combining GH with IGF-I. Randomized studies of GH therapy in catabolic states, with targeted dosing and longer duration of treatment are required to fully assess the safety and efficacy of this treatment approach.

العلاقة: firstpage:219; lastpage:226; numberofpages:8; journal:JOURNAL OF CARDIAC FAILURE; http://hdl.handle.net/11562/30712Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0037599468

الإتاحة: http://hdl.handle.net/11562/30712Test