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

dc.contributor.authorNoblet, Jillian N.
dc.contributor.authorGoodwill, Adam G.
dc.contributor.authorSassoon, Daniel J.
dc.contributor.authorKiel, Alexander M.
dc.contributor.authorTune, Johnathan D.
dc.contributor.departmentDepartment of Cellular & Integrative Physiology, IU School of Medicineen_US
dc.date.accessioned2017-08-03T13:29:23Z
dc.date.available2017-08-03T13:29:23Z
dc.date.issued2016-05
dc.description.abstractLeptin 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.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationNoblet, J. N., Goodwill, A. G., Sassoon, D. J., Kiel, A. M., & Tune, J. D. (2016). Leptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho kinase dependent pathway. Basic Research in Cardiology, 111(3), 25. http://doi.org/10.1007/s00395-016-0545-6en_US
dc.identifier.urihttps://hdl.handle.net/1805/13747
dc.language.isoen_USen_US
dc.publisherSpringeren_US
dc.relation.isversionof10.1007/s00395-016-0545-6en_US
dc.relation.journalBasic Research in Cardiologyen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectLeptinen_US
dc.subjectRho kinaseen_US
dc.subjectCoronaryen_US
dc.titleLeptin augments coronary vasoconstriction and smooth muscle proliferation via a Rho-kinase-dependent pathwayen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
nihms-823909.pdf
Size:
1.53 MB
Format:
Adobe Portable Document Format
Description:
Main Article
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.88 KB
Format:
Item-specific license agreed upon to submission
Description: