Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle: Influence of obesity

Meredith Kohr Owen, Frank Witzmann, Mikaela L. Mckenney, Xianyin Lai, Zachary C. Berwick, Steven P. Moberly, Mouhamad Alloosh, Michael Sturek, Johnathan Tune

Research output: Contribution to journalArticle

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Abstract

BACKGROUND - : This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)-derived factors influence vasomotor tone and the PVAT proteome in lean versus obese swine. METHODS AND RESULTS - : Coronary arteries from Ossabaw swine were isolated for isometric tension studies. We found that coronary (P=0.03) and mesenteric (P=0.04) but not subcutaneous adipose tissue augmented coronary contractions to KCl (20 mmol/L). Inhibition of CaV1.2 channels with nifedipine (0.1 μmol/L) or diltiazem (10 μmol/L) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to prostaglandin F2α in proportion to the amount of PVAT present (0.1-1.0 g). These effects were elevated in tissues obtained from obese swine and were observed in intact and endothelium denuded arteries. Coronary PVAT also diminished H2O2-mediated vasodilation in lean and, to a lesser extent, in obese arteries. These effects were associated with alterations in the obese coronary PVAT proteome (detected 186 alterations) and elevated voltage-dependent increases in intracellular [Ca] in obese smooth muscle cells. Further studies revealed that the Rho-kinase inhibitor fasudil (1 μmol/L) significantly blunted artery contractions to KCl and PVAT in lean but not obese swine. Calpastatin (10 μmol/L) also augmented contractions to levels similar to that observed in the presence of PVAT. CONCLUSIONS - : Vascular effects of PVAT vary according to anatomic location and are influenced by an obese phenotype. Augmented contractile effects of obese coronary PVAT are related to alterations in the PVAT proteome (eg, calpastatin), Rho-dependent signaling, and the functional contribution of K and CaV1.2 channels to smooth muscle tone.

Original languageEnglish
Pages (from-to)9-18
Number of pages10
JournalCirculation
Volume128
Issue number1
DOIs
StatePublished - Jul 2 2013

Fingerprint

Vascular Smooth Muscle
Adipose Tissue
Obesity
Swine
Proteome
Arteries
rho-Associated Kinases
Dinoprost
Diltiazem
Subcutaneous Fat
Thromboplastin
Nifedipine
Constriction
Vasodilation
Smooth Muscle Myocytes
Endothelium
Smooth Muscle
Blood Vessels
Coronary Vessels
Phenotype

Keywords

  • adipose tissue
  • coronary disease
  • muscle, smooth
  • obesity
  • vasoconstriction

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle : Influence of obesity. / Owen, Meredith Kohr; Witzmann, Frank; Mckenney, Mikaela L.; Lai, Xianyin; Berwick, Zachary C.; Moberly, Steven P.; Alloosh, Mouhamad; Sturek, Michael; Tune, Johnathan.

In: Circulation, Vol. 128, No. 1, 02.07.2013, p. 9-18.

Research output: Contribution to journalArticle

Owen, Meredith Kohr ; Witzmann, Frank ; Mckenney, Mikaela L. ; Lai, Xianyin ; Berwick, Zachary C. ; Moberly, Steven P. ; Alloosh, Mouhamad ; Sturek, Michael ; Tune, Johnathan. / Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle : Influence of obesity. In: Circulation. 2013 ; Vol. 128, No. 1. pp. 9-18.
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abstract = "BACKGROUND - : This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)-derived factors influence vasomotor tone and the PVAT proteome in lean versus obese swine. METHODS AND RESULTS - : Coronary arteries from Ossabaw swine were isolated for isometric tension studies. We found that coronary (P=0.03) and mesenteric (P=0.04) but not subcutaneous adipose tissue augmented coronary contractions to KCl (20 mmol/L). Inhibition of CaV1.2 channels with nifedipine (0.1 μmol/L) or diltiazem (10 μmol/L) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to prostaglandin F2α in proportion to the amount of PVAT present (0.1-1.0 g). These effects were elevated in tissues obtained from obese swine and were observed in intact and endothelium denuded arteries. Coronary PVAT also diminished H2O2-mediated vasodilation in lean and, to a lesser extent, in obese arteries. These effects were associated with alterations in the obese coronary PVAT proteome (detected 186 alterations) and elevated voltage-dependent increases in intracellular [Ca] in obese smooth muscle cells. Further studies revealed that the Rho-kinase inhibitor fasudil (1 μmol/L) significantly blunted artery contractions to KCl and PVAT in lean but not obese swine. Calpastatin (10 μmol/L) also augmented contractions to levels similar to that observed in the presence of PVAT. CONCLUSIONS - : Vascular effects of PVAT vary according to anatomic location and are influenced by an obese phenotype. Augmented contractile effects of obese coronary PVAT are related to alterations in the PVAT proteome (eg, calpastatin), Rho-dependent signaling, and the functional contribution of K and CaV1.2 channels to smooth muscle tone.",
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T1 - Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle

T2 - Influence of obesity

AU - Owen, Meredith Kohr

AU - Witzmann, Frank

AU - Mckenney, Mikaela L.

AU - Lai, Xianyin

AU - Berwick, Zachary C.

AU - Moberly, Steven P.

AU - Alloosh, Mouhamad

AU - Sturek, Michael

AU - Tune, Johnathan

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N2 - BACKGROUND - : This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)-derived factors influence vasomotor tone and the PVAT proteome in lean versus obese swine. METHODS AND RESULTS - : Coronary arteries from Ossabaw swine were isolated for isometric tension studies. We found that coronary (P=0.03) and mesenteric (P=0.04) but not subcutaneous adipose tissue augmented coronary contractions to KCl (20 mmol/L). Inhibition of CaV1.2 channels with nifedipine (0.1 μmol/L) or diltiazem (10 μmol/L) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to prostaglandin F2α in proportion to the amount of PVAT present (0.1-1.0 g). These effects were elevated in tissues obtained from obese swine and were observed in intact and endothelium denuded arteries. Coronary PVAT also diminished H2O2-mediated vasodilation in lean and, to a lesser extent, in obese arteries. These effects were associated with alterations in the obese coronary PVAT proteome (detected 186 alterations) and elevated voltage-dependent increases in intracellular [Ca] in obese smooth muscle cells. Further studies revealed that the Rho-kinase inhibitor fasudil (1 μmol/L) significantly blunted artery contractions to KCl and PVAT in lean but not obese swine. Calpastatin (10 μmol/L) also augmented contractions to levels similar to that observed in the presence of PVAT. CONCLUSIONS - : Vascular effects of PVAT vary according to anatomic location and are influenced by an obese phenotype. Augmented contractile effects of obese coronary PVAT are related to alterations in the PVAT proteome (eg, calpastatin), Rho-dependent signaling, and the functional contribution of K and CaV1.2 channels to smooth muscle tone.

AB - BACKGROUND - : This investigation examined the mechanisms by which coronary perivascular adipose tissue (PVAT)-derived factors influence vasomotor tone and the PVAT proteome in lean versus obese swine. METHODS AND RESULTS - : Coronary arteries from Ossabaw swine were isolated for isometric tension studies. We found that coronary (P=0.03) and mesenteric (P=0.04) but not subcutaneous adipose tissue augmented coronary contractions to KCl (20 mmol/L). Inhibition of CaV1.2 channels with nifedipine (0.1 μmol/L) or diltiazem (10 μmol/L) abolished this effect. Coronary PVAT increased baseline tension and potentiated constriction of isolated arteries to prostaglandin F2α in proportion to the amount of PVAT present (0.1-1.0 g). These effects were elevated in tissues obtained from obese swine and were observed in intact and endothelium denuded arteries. Coronary PVAT also diminished H2O2-mediated vasodilation in lean and, to a lesser extent, in obese arteries. These effects were associated with alterations in the obese coronary PVAT proteome (detected 186 alterations) and elevated voltage-dependent increases in intracellular [Ca] in obese smooth muscle cells. Further studies revealed that the Rho-kinase inhibitor fasudil (1 μmol/L) significantly blunted artery contractions to KCl and PVAT in lean but not obese swine. Calpastatin (10 μmol/L) also augmented contractions to levels similar to that observed in the presence of PVAT. CONCLUSIONS - : Vascular effects of PVAT vary according to anatomic location and are influenced by an obese phenotype. Augmented contractile effects of obese coronary PVAT are related to alterations in the PVAT proteome (eg, calpastatin), Rho-dependent signaling, and the functional contribution of K and CaV1.2 channels to smooth muscle tone.

KW - adipose tissue

KW - coronary disease

KW - muscle, smooth

KW - obesity

KW - vasoconstriction

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