This Program Project retains as its theme the investigation of interacting mechanisms that regulate vascular smooth muscle cell (VSMC) proliferation and extracellular matrix production. These features are central to the development of atherosclerotic lesions. Dr. Gail Sonenshein (Project 1) will extend her findings on the roles of the myb family and NFkB in the coordinated regulation of collagen and elastin gene expression and VSMC proliferation. The mechanism of repression of matrix gene transcription by B-Myb and the roles of phosphorylation and protein interactions will be investigated. Dr. Katya Ravid (Project 2) will investigate the regulation of expression of the A2bAR gene and the role of B-Myb in proliferation-induced upregulation of this gene. She will also identify the role of this receptor in vascular function, focusing on VSMC proliferation, matrix production and vascular tone. Dr. Herbert Kagan (Project 3), will be concerned with the interactions recently found in his laboratory between lysyl oxidase (LO), the extrecellular connective tissue crosslinking enzyme, and surface membrane integrins and nuclei of VSMC. The receptors and mechanisms involved in the induction by LO of VSMC chemotaxis, suppression of cell proliferation and stimulation of collagen production will be investigated. Dr. Barbara Smith (Project 4), a new Project Leader in this Program Project, will extend her transcription. She has recently identified a transcription co-regulator (CIITA) that is induced during inflammation and acts to decrease collagen transcription. She will also investigate the role of statins in collagen gene transcription. She will also investigate the role of statins in collagen gene transcription. Overall, the research of this Program Project will be conducted with VSMCs in vitro and with transgenic mouse models of vascular injury. The program is supported by an Administrative Core and a BioModel Core. The BioModel Core, directed by Dr. Barbara Schreiber, provides a variety of services to support these projects. Of particular note, Dr. Schreiber has introduced a mouse femoral artery injury model with generates restenotic and atherosclerotic-like lesions. Each project will avail itself of this model to test hypotheses in vivo.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL013262-33
Application #
7413538
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2006-09-01
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
33
Fiscal Year
2006
Total Cost
$307,943
Indirect Cost
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Lucero, Héctor A; Mäki, Joni M; Kagan, Herbert M (2011) Activation of cellular chemotactic responses to chemokines coupled with oxidation of plasma membrane proteins by lysyl oxidase. J Neural Transm (Vienna) 118:1091-9
Chen, Hongjie; Koupenova, Milka; Yang, Dan et al. (2011) Regulation of MMP-9 expression by the A2b adenosine receptor and its dependency on TNF-? signaling. Exp Hematol 39:525-30
Yang, D; Chen, H; Koupenova, M et al. (2010) A new role for the A2b adenosine receptor in regulating platelet function. J Thromb Haemost 8:817-27
Grimsby, Jessica L; Lucero, Hector A; Trackman, Philip C et al. (2010) Role of lysyl oxidase propeptide in secretion and enzyme activity. J Cell Biochem 111:1231-43
St Hilaire, Cynthia; Carroll, Shannon H; Chen, Hongjie et al. (2009) Mechanisms of induction of adenosine receptor genes and its functional significance. J Cell Physiol 218:35-44
Wu, Xiaoyan; Kong, Xiaocen; Luchsinger, Larry et al. (2009) Regulating the activity of class II transactivator by posttranslational modifications: exploring the possibilities. Mol Cell Biol 29:5639-44
Chen, Hongjie; Yang, Dan; Carroll, Shannon H et al. (2009) Activation of the macrophage A2b adenosine receptor regulates tumor necrosis factor-alpha levels following vascular injury. Exp Hematol 37:533-8
Chandrasekharan, Bindu P; Kolachala, Vasantha L; Dalmasso, Guillaume et al. (2009) Adenosine 2B receptors (A(2B)AR) on enteric neurons regulate murine distal colonic motility. FASEB J 23:2727-34
St Hilaire, Cynthia; Koupenova, Milka; Carroll, Shannon H et al. (2008) TNF-alpha upregulates the A2B adenosine receptor gene: The role of NAD(P)H oxidase 4. Biochem Biophys Res Commun 375:292-6
Lucero, Hector A; Ravid, Katya; Grimsby, Jessica L et al. (2008) Lysyl oxidase oxidizes cell membrane proteins and enhances the chemotactic response of vascular smooth muscle cells. J Biol Chem 283:24103-17

Showing the most recent 10 out of 164 publications