Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathway

Jillian N. Noblet, Adam G. Goodwill, Daniel J. Sassoon, Alexander M. Kiel, Johnathan D. Tune

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Leptin has been implicated as a key upstream mediator of pathways associated with coronary vascular dysfunction and disease. The purpose of this investigation was to test the hypothesis that leptin modifies the coronary artery proteome and promotes increases in coronary smooth muscle contraction and proliferation via influences on Rho kinase signaling. Global proteomic assessment of coronary arteries from lean swine cultured with obese concentrations of leptin (30 ng/mL) for 3 days revealed significant alterations in the coronary artery proteome (68 proteins) and identified an association between leptin treatment and calcium signaling/contraction (four proteins) and cellular growth and proliferation (35 proteins). Isometric tension studies demonstrated that both acute (30 min) and chronic (3 days, serum-free media) exposure to obese concentrations of leptin potentiated depolarization-induced contraction of coronary arteries. Inhibition of Rho kinase significantly reduced leptin-mediated increases in coronary artery contractions. The effects of leptin on the functional expression of Rho kinase were time-dependent, as acute treatment increased Rho kinase activity while chronic (3 day) exposure was associated with increases in Rho kinase protein abundance. Proliferation assays following chronic leptin administration (8 day, serum-containing media) demonstrated that leptin augmented coronary vascular smooth muscle proliferation and increased Rho kinase activity. Inhibition of Rho kinase significantly reduced these effects of leptin. Taken together, these findings demonstrate that leptin promotes increases in coronary vasoconstriction and smooth muscle proliferation and indicate that these phenotypic effects are associated with alterations in the coronary artery proteome and dynamic effects on the Rho kinase pathway.

Original languageEnglish (US)
Article number25
JournalBasic Research in Cardiology
Volume111
Issue number3
DOIs
StatePublished - May 1 2016

Fingerprint

rho-Associated Kinases
Leptin
Vasoconstriction
Smooth Muscle
Coronary Vessels
Proteome
Proteins
Calcium Signaling
Serum-Free Culture Media
Muscle Contraction
Vascular Diseases
Vascular Smooth Muscle
Proteomics
Coronary Disease
Swine
Cell Proliferation

Keywords

  • Coronary
  • Leptin
  • Rho kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathway. / Noblet, Jillian N.; Goodwill, Adam G.; Sassoon, Daniel J.; Kiel, Alexander M.; Tune, Johnathan D.

In: Basic Research in Cardiology, Vol. 111, No. 3, 25, 01.05.2016.

Research output: Contribution to journalArticle

Noblet, Jillian N. ; Goodwill, Adam G. ; Sassoon, Daniel J. ; Kiel, Alexander M. ; Tune, Johnathan D. / Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathway. In: Basic Research in Cardiology. 2016 ; Vol. 111, No. 3.
@article{f2b8eda8636e46cca6fb9c5e660d384b,
title = "Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathway",
abstract = "Leptin has been implicated as a key upstream mediator of pathways associated with coronary vascular dysfunction and disease. The purpose of this investigation was to test the hypothesis that leptin modifies the coronary artery proteome and promotes increases in coronary smooth muscle contraction and proliferation via influences on Rho kinase signaling. Global proteomic assessment of coronary arteries from lean swine cultured with obese concentrations of leptin (30 ng/mL) for 3 days revealed significant alterations in the coronary artery proteome (68 proteins) and identified an association between leptin treatment and calcium signaling/contraction (four proteins) and cellular growth and proliferation (35 proteins). Isometric tension studies demonstrated that both acute (30 min) and chronic (3 days, serum-free media) exposure to obese concentrations of leptin potentiated depolarization-induced contraction of coronary arteries. Inhibition of Rho kinase significantly reduced leptin-mediated increases in coronary artery contractions. The effects of leptin on the functional expression of Rho kinase were time-dependent, as acute treatment increased Rho kinase activity while chronic (3 day) exposure was associated with increases in Rho kinase protein abundance. Proliferation assays following chronic leptin administration (8 day, serum-containing media) demonstrated that leptin augmented coronary vascular smooth muscle proliferation and increased Rho kinase activity. Inhibition of Rho kinase significantly reduced these effects of leptin. Taken together, these findings demonstrate that leptin promotes increases in coronary vasoconstriction and smooth muscle proliferation and indicate that these phenotypic effects are associated with alterations in the coronary artery proteome and dynamic effects on the Rho kinase pathway.",
keywords = "Coronary, Leptin, Rho kinase",
author = "Noblet, {Jillian N.} and Goodwill, {Adam G.} and Sassoon, {Daniel J.} and Kiel, {Alexander M.} and Tune, {Johnathan D.}",
year = "2016",
month = "5",
day = "1",
doi = "10.1007/s00395-016-0545-6",
language = "English (US)",
volume = "111",
journal = "Basic Research in Cardiology",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "3",

}

TY - JOUR

T1 - Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathway

AU - Noblet, Jillian N.

AU - Goodwill, Adam G.

AU - Sassoon, Daniel J.

AU - Kiel, Alexander M.

AU - Tune, Johnathan D.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Leptin has been implicated as a key upstream mediator of pathways associated with coronary vascular dysfunction and disease. The purpose of this investigation was to test the hypothesis that leptin modifies the coronary artery proteome and promotes increases in coronary smooth muscle contraction and proliferation via influences on Rho kinase signaling. Global proteomic assessment of coronary arteries from lean swine cultured with obese concentrations of leptin (30 ng/mL) for 3 days revealed significant alterations in the coronary artery proteome (68 proteins) and identified an association between leptin treatment and calcium signaling/contraction (four proteins) and cellular growth and proliferation (35 proteins). Isometric tension studies demonstrated that both acute (30 min) and chronic (3 days, serum-free media) exposure to obese concentrations of leptin potentiated depolarization-induced contraction of coronary arteries. Inhibition of Rho kinase significantly reduced leptin-mediated increases in coronary artery contractions. The effects of leptin on the functional expression of Rho kinase were time-dependent, as acute treatment increased Rho kinase activity while chronic (3 day) exposure was associated with increases in Rho kinase protein abundance. Proliferation assays following chronic leptin administration (8 day, serum-containing media) demonstrated that leptin augmented coronary vascular smooth muscle proliferation and increased Rho kinase activity. Inhibition of Rho kinase significantly reduced these effects of leptin. Taken together, these findings demonstrate that leptin promotes increases in coronary vasoconstriction and smooth muscle proliferation and indicate that these phenotypic effects are associated with alterations in the coronary artery proteome and dynamic effects on the Rho kinase pathway.

AB - Leptin has been implicated as a key upstream mediator of pathways associated with coronary vascular dysfunction and disease. The purpose of this investigation was to test the hypothesis that leptin modifies the coronary artery proteome and promotes increases in coronary smooth muscle contraction and proliferation via influences on Rho kinase signaling. Global proteomic assessment of coronary arteries from lean swine cultured with obese concentrations of leptin (30 ng/mL) for 3 days revealed significant alterations in the coronary artery proteome (68 proteins) and identified an association between leptin treatment and calcium signaling/contraction (four proteins) and cellular growth and proliferation (35 proteins). Isometric tension studies demonstrated that both acute (30 min) and chronic (3 days, serum-free media) exposure to obese concentrations of leptin potentiated depolarization-induced contraction of coronary arteries. Inhibition of Rho kinase significantly reduced leptin-mediated increases in coronary artery contractions. The effects of leptin on the functional expression of Rho kinase were time-dependent, as acute treatment increased Rho kinase activity while chronic (3 day) exposure was associated with increases in Rho kinase protein abundance. Proliferation assays following chronic leptin administration (8 day, serum-containing media) demonstrated that leptin augmented coronary vascular smooth muscle proliferation and increased Rho kinase activity. Inhibition of Rho kinase significantly reduced these effects of leptin. Taken together, these findings demonstrate that leptin promotes increases in coronary vasoconstriction and smooth muscle proliferation and indicate that these phenotypic effects are associated with alterations in the coronary artery proteome and dynamic effects on the Rho kinase pathway.

KW - Coronary

KW - Leptin

KW - Rho kinase

UR - http://www.scopus.com/inward/record.url?scp=84960982029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960982029&partnerID=8YFLogxK

U2 - 10.1007/s00395-016-0545-6

DO - 10.1007/s00395-016-0545-6

M3 - Article

C2 - 26975316

AN - SCOPUS:84960982029

VL - 111

JO - Basic Research in Cardiology

JF - Basic Research in Cardiology

SN - 0300-8428

IS - 3

M1 - 25

ER -