Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice

Sander S. Rensen, Petra M. Niessen, Jan Van Deursen, Ben J. Janssen, Edwin Heijman, Evelien Hermeling, Merlijn Meens, Natascha Lie, Marion J. Gijbels, Gustav J. Strijkers, Pieter A. Doevendans, Marten H. Hofker, Jo G R De Mey, Guillaume J. Van Eys

Research output: Contribution to journalArticle

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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 -/-). Methods and 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, α-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.

Original languageEnglish (US)
Pages (from-to)828-836
Number of pages9
JournalCirculation
Volume118
Issue number8
DOIs
StatePublished - Aug 19 2008

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Cardiomegaly
Hypertension
Smooth Muscle
Arteries
Smooth Muscle Myocytes
Smooth Muscle Myosins
Phenotype
Microfilament Proteins
Pulse Wave Analysis
Myosin Heavy Chains
Femoral Artery
Muscle Contraction
Genes
Blood Vessels
Aorta
Actins
Arterial Pressure
Magnetic Resonance Imaging
Blood Pressure
Mutation

Keywords

  • Hypertension
  • Hypertrophy
  • Muscle
  • Muscle contraction
  • Smooth
  • Vascular resistance

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice. / Rensen, Sander S.; Niessen, Petra M.; Van Deursen, Jan; Janssen, Ben J.; Heijman, Edwin; Hermeling, Evelien; Meens, Merlijn; Lie, Natascha; Gijbels, Marion J.; Strijkers, Gustav J.; Doevendans, Pieter A.; Hofker, Marten H.; De Mey, Jo G R; Van Eys, Guillaume J.

In: Circulation, Vol. 118, No. 8, 19.08.2008, p. 828-836.

Research output: Contribution to journalArticle

Rensen, SS, Niessen, PM, Van Deursen, J, Janssen, BJ, Heijman, E, Hermeling, E, Meens, M, Lie, N, Gijbels, MJ, Strijkers, GJ, Doevendans, PA, Hofker, MH, De Mey, JGR & Van Eys, GJ 2008, 'Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice', Circulation, vol. 118, no. 8, pp. 828-836. https://doi.org/10.1161/CIRCULATIONAHA.107.743690
Rensen, Sander S. ; Niessen, Petra M. ; Van Deursen, Jan ; Janssen, Ben J. ; Heijman, Edwin ; Hermeling, Evelien ; Meens, Merlijn ; Lie, Natascha ; Gijbels, Marion J. ; Strijkers, Gustav J. ; Doevendans, Pieter A. ; Hofker, Marten H. ; De Mey, Jo G R ; Van Eys, Guillaume J. / Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice. In: Circulation. 2008 ; Vol. 118, No. 8. pp. 828-836.
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T1 - Smoothelin-B deficiency results in reduced arterial contractility, hypertension, and cardiac hypertrophy in mice

AU - Rensen, Sander S.

AU - Niessen, Petra M.

AU - Van Deursen, Jan

AU - Janssen, Ben J.

AU - Heijman, Edwin

AU - Hermeling, Evelien

AU - Meens, Merlijn

AU - Lie, Natascha

AU - Gijbels, Marion J.

AU - Strijkers, Gustav J.

AU - Doevendans, Pieter A.

AU - Hofker, Marten H.

AU - De Mey, Jo G R

AU - Van Eys, Guillaume J.

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N2 - 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 -/-). Methods and 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, α-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.

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KW - Hypertension

KW - Hypertrophy

KW - Muscle

KW - Muscle contraction

KW - Smooth

KW - Vascular resistance

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