title: Angiogenesis-related factors in skeletal muscles of COPD patients: roles of angiopoietin-2.
abstract: The role of angiogenesis factors in skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) is unknown. The first objective of this study was to assess various pro- and antiangiogenic factor and receptor expressions in the vastus lateralis muscles of control subjects and COPD patients. Preliminary inquiries revealed that angiopoietin-2 (ANGPT2) is overexpressed in limb muscles of COPD patients. ANGPT2 promotes skeletal satellite cell survival and differentiation. Factors that are involved in regulating muscle ANGPT2 production are unknown. The second objective of this study was to evaluate how oxidants and proinflammatory cytokines influence muscle-derived ANGPT2 expression. Angiogenic gene expressions in human vastus lateralis biopsies were quantified with low-density real-time PCR arrays. ANGPT2 mRNA expressions in cultured skeletal myoblasts were quantified in response to proinflammatory cytokine and H2O2 exposure. Ten proangiogenesis genes, including ANGPT2, were significantly upregulated in the vastus lateralis muscles of COPD patients. ANGPT2 mRNA levels correlated negatively with forced expiratory volume in 1 s and positively with muscle wasting. Immunoblotting confirmed that ANGPT2 protein levels were significantly greater in muscles of COPD patients compared with control subjects. ANGPT2 expression was induced by interferon-γ and -β and by hydrogen peroxide, but not by tumor necrosis factor. We conclude that upregulation of ANGPT2 expression in vastus lateralis muscles of COPD patients is likely due to oxidative stress and represents a positive adaptive response aimed at facilitating myogenesis and angiogenesis.
authors.affiliation: Department of Critical Care, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Mahroo
authors.initials: M
authors.lastname: Mofarrahi
authors.forename: Ioanna
authors.initials: I
authors.lastname: Sigala
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilokopoulos
authors.forename: Sharon
authors.initials: S
authors.lastname: Harel
authors.forename: Yeting
authors.initials: Y
authors.lastname: Guo
authors.forename: Richard
authors.initials: R
authors.lastname: Debigare
authors.forename: Francois
authors.initials: F
authors.lastname: Maltais
authors.forename: Sabah N A
authors.initials: SN
authors.lastname: Hussain
mesh_terms: D000368:Aged; D042501:Angiogenic Proteins / Q000235:genetics / Q000502:physiology; D042702:Angiopoietin-2 / Q000235:genetics / Q000502:physiology*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003964:Diaphragm / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000235:genetics; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D042501:Angiogenic Proteins; D042702:Angiopoietin-2; D016207:Cytokines; D012333:RNA, Messenger
keywords: COPD; angiogenesis; angiopoietins; cytokines; myogenesis; skeletal muscles