title: ACE inhibition modifies exercise-induced pro-angiogenic and mitochondrial gene transcript expression.
abstract: Skeletal muscle responds to endurance exercise with an improvement of biochemical pathways that support substrate supply and oxygen-dependent metabolism. This is reflected by enhanced expression of associated factors after exercise and is specifically modulated by tissue perfusion and oxygenation. We hypothesized that transcript expression of pro-angiogenic factors (VEGF, tenascin-C, Angpt1, Angpt1R) and oxygen metabolism (COX4I1, COX4I2, HIF-1α) in human muscle after an endurance stimulus depends on vasoconstriction, and would be modulated through angiotensin-converting enzyme inhibition by intake of lisinopril. Fourteen non-specifically trained, male Caucasians subjects, carried out a single bout of standardized one-legged bicycle exercise. Seven of the participants consumed lisinopril in the 3 days before exercise. Biopsies were collected pre- and 3 h post-exercise from the m. vastus lateralis. COX4I1 (P = 0.03), COX4I2 (P = 0.04) mRNA and HIF-1α (P = 0.05) mRNA and protein levels (P = 0.01) showed an exercise-induced increase in the group not consuming the ACE inhibitor. Conversely, there was a specific exercise-induced increase in VEGF transcript (P = 0.04) and protein levels (P = 0.03) and a trend for increased tenascin-c transcript levels (P = 0.09) for subjects consuming lisinopril. The observations indicate that exercise-induced expression of transcripts involved in angiogenesis and mitochondrial energy metabolism are to some extent regulated via a hypoxia-related ACE-dependent mechanism.
authors.affiliation: School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.|MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: van Ginkel
authors.affiliation: University Hospital Balgrist, Laboratory for Muscle Plasticity, University of Zurich, Zurich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Ruoss
authors.affiliation: University Hospital Balgrist, Laboratory for Muscle Plasticity, University of Zurich, Zurich, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Valdivieso
authors.affiliation: School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.
authors.forename: H
authors.initials: H
authors.lastname: Degens
authors.affiliation: School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Waldron
authors.affiliation: School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.|MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: de Haan
authors.affiliation: University Hospital Balgrist, Laboratory for Muscle Plasticity, University of Zurich, Zurich, Switzerland. mflueck@research.balgrist.ch.
authors.forename: M
authors.initials: M
authors.lastname: Flück
mesh_terms: D000328:Adult; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052097:Quadriceps Muscle / Q000502:physiology; D012313:RNA / Q000378:metabolism*; D000077278:RNA, Mitochondrial; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D000806:Angiotensin-Converting Enzyme Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000077278:RNA, Mitochondrial; D019063:Tenascin; D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D017706:Lisinopril; C000616975:COX4I1 protein, human; C539675:COX4I2 protein, human; D003576:Electron Transport Complex IV
keywords: Muscle; angiotensin; exercise; gene; hypertension; hypoxia; lisinopril; perfusion