title: Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice.
abstract: BACKGROUND
  Smoothelins are actin-binding proteins that are abundantly expressed in healthy visceral (smoothelin-A) and vascular (smoothelin-B) smooth muscle. Their expression is strongly associated with the contractile phenotype of smooth muscle cells. Analysis of mice lacking both smoothelins (Smtn-A/B(-/-) mice) previously revealed a critical role for smoothelin-A in intestinal smooth muscle contraction. Here, we report on the generation and cardiovascular phenotype of mice lacking only smoothelin-B (Smtn-B(-/-)).
  
  
  RESULTS
  Myograph studies revealed that the contractile capacity of the saphenous and femoral arteries was strongly reduced in Smtn-B(-/-) mice, regardless of the contractile agonist used to trigger contraction. Arteries from Smtn-A/B(-/-) compound mutant mice exhibited a similar contractile deficit. Smtn-B(-/-) arteries had a normal architecture and expressed normal levels of other smooth muscle cell-specific genes, including smooth muscle myosin heavy chain, alpha-smooth muscle actin, and smooth muscle-calponin. Decreased contractility of Smtn-B(-/-) arteries was paradoxically accompanied by increased mean arterial pressure (20 mm Hg) and concomitant cardiac hypertrophy despite normal parasympathetic and sympathetic tone in Smtn-B(-/-) mice. Magnetic resonance imaging experiments revealed that cardiac function was not changed, whereas distension of the proximal aorta during the cardiac cycle was increased in Smtn-B(-/-) mice. However, isobaric pulse wave velocity and pulse pressure measurements indicated normal aortic distensibility.
  
  
  CONCLUSIONS
  Collectively, our results identify smoothelins as key determinants of arterial smooth muscle contractility and cardiovascular performance. Studies on mutations in the Smtn gene or alterations in smoothelin levels in connection to hypertension in humans are warranted.
authors.affiliation: Department of Genetics and Cell Biology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: Sander S
authors.initials: SS
authors.lastname: Rensen
authors.forename: Petra M
authors.initials: PM
authors.lastname: Niessen
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Deursen
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Janssen
authors.forename: Edwin
authors.initials: E
authors.lastname: Heijman
authors.forename: Evelien
authors.initials: E
authors.lastname: Hermeling
authors.forename: Merlijn
authors.initials: M
authors.lastname: Meens
authors.forename: Natascha
authors.initials: N
authors.lastname: Lie
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
authors.forename: Guillaume J
authors.initials: GJ
authors.lastname: van Eys
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology*; D006332:Cardiomegaly / Q000209:etiology*; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000502:physiology; D006973:Hypertension / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D014655:Vascular Resistance; D014661:Vasoconstriction
chemical_list: D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; C491050:Smtn protein, mouse