The proposed research program focuses on diacylglycerol formation in vascular smooth muscle. Diacylglycerol (DG), one of the major putative second messengers of the phosphoinositide system, will be measured in both cultured vascular smooth muscle cells (VSMC) and intact rat aorta. Biochemical and physiological mechanisms controlling agonist-induced DG formation will be defined, and the role of DG in sustaining vascular smooth muscle contraction will be examined. Radioisotopic labelling, subcellular fractionation, and chromatogtaphic separation will be used to quantitate and localize lipids, and measurement of isometric force developed by ring segments of aorta will be used to quantitate contraction.
Specific aims i nclude: 1) determining the ionic and endocytotic mechanisms controlling sustained angiotensin II-induced DG formation in VSMC; 2) characterizing angiotensin II- and norepinephrine-stimulated phosphoinositide hydrolysis and DG production in intact rat aorta and comparing it with that produced by angiotensin II in VSMC; 3) determining the physiological or biochemical bases for any observed differences in phosphoinositide metabolism between cultured cells and intact aorta; and 4) determining whether DG/protein kinase C has a role in sustaining vascular smooth muscle contraction. These studies should provide important basic information on the cellular mechanisms controlling the sustained phosphoinositide response in vascular smooth muscle and their relationship to contraction. Understanding the mechanisms of normal vascular responsiveness should provide insight into the pathophysiology of hypertension and atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL038206-06
Application #
3470994
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1988-07-01
Project End
1992-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Fujii, Masakazu; Amanso, Angélica; Abrahão, Thalita B et al. (2016) Polymerase delta-interacting protein 2 regulates collagen accumulation via activation of the Akt/mTOR pathway in vascular smooth muscle cells. J Mol Cell Cardiol 92:21-9
Brown, David I; Griendling, Kathy K (2015) Regulation of signal transduction by reactive oxygen species in the cardiovascular system. Circ Res 116:531-49
Abrahao, Thalita B; Griendling, Kathy K (2015) Nuclear factor (erythroid-derived 2)-like 2, the brake in oxidative stress that nicotinamide adenine dinucleotide phosphate-oxidase-4 needs to protect the heart. Hypertension 65:499-501
Datla, Srinivasa Raju; McGrail, Daniel J; Vukelic, Sasa et al. (2014) Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization. Am J Physiol Heart Circ Physiol 307:H945-57
Brown, David I; Lassègue, Bernard; Lee, Minyoung et al. (2014) Poldip2 knockout results in perinatal lethality, reduced cellular growth and increased autophagy of mouse embryonic fibroblasts. PLoS One 9:e96657
Vukelic, Sasa; Griendling, Kathy K (2014) Angiotensin II, from vasoconstrictor to growth factor: a paradigm shift. Circ Res 114:754-7
Amanso, Angélica M; Lassègue, Bernard; Joseph, Giji et al. (2014) Polymerase ?-interacting protein 2 promotes postischemic neovascularization of the mouse hindlimb. Arterioscler Thromb Vasc Biol 34:1548-55
Sutliff, Roy L; Hilenski, Lula L; Amanso, Angélica M et al. (2013) Polymerase delta interacting protein 2 sustains vascular structure and function. Arterioscler Thromb Vasc Biol 33:2154-61
Martin-Garrido, Abel; Williams, Holly C; Lee, Minyoung et al. (2013) Transforming growth factor ? inhibits platelet derived growth factor-induced vascular smooth muscle cell proliferation via Akt-independent, Smad-mediated cyclin D1 downregulation. PLoS One 8:e79657
Williams, Holly C; San Martín, Alejandra; Adamo, Candace M et al. (2012) Role of coronin 1B in PDGF-induced migration of vascular smooth muscle cells. Circ Res 111:56-65

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