Neil J. Freedman

Journal article Arterioscler Thromb Vasc Biol · November 2010 Featured Publication OBJECTIVE: To accelerate vein graft reendothelialization and reduce vein graft thrombosis by infusing human umbilical cord blood-derived endothelial cells (hCB-ECs) because loss of endothelium contributes to vein graft thrombosis and neointimal hyperplasia ... Full text Open Access Link to item Cite

Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and human association studies.

Journal article Hum Mol Genet · July 15, 2010 Featured Publication Aging is believed to be among the most important contributors to atherosclerosis, through mechanisms that remain largely obscure. Serum levels of tumor necrosis factor (TNF) rise with aging and have been correlated with the incidence of myocardial infarcti ... Full text Open Access Link to item Cite

Reciprocal regulation of the platelet-derived growth factor receptor-beta and G protein-coupled receptor kinase 5 by cross-phosphorylation: effects on catalysis.

Journal article Mol Pharmacol · March 2009 Featured Publication Signaling by the platelet-derived growth factor receptor-beta (PDGFRbeta) is diminished when the PDGFRbeta is phosphorylated on seryl residues by G protein-coupled receptor kinase-5 (GRK5), but mechanisms for GRK5 activation by the PDGFRbeta remain obscure ... Full text Link to item Cite

Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis.

Journal article PLoS Genet · January 2009 Featured Publication Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in ... Full text Open Access Link to item Cite

Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration.

Journal article Circ Res · July 3, 2008 Featured Publication Atherosclerosis and arterial injury-induced neointimal hyperplasia involve medial smooth muscle cell (SMC) proliferation and migration into the arterial intima. Because many 7-transmembrane and growth factor receptors promote atherosclerosis, we hypothesiz ... Full text Open Access Link to item Cite

Tumor necrosis factor receptor-2 signaling attenuates vein graft neointima formation by promoting endothelial recovery.

Journal article Arterioscler Thromb Vasc Biol · February 2008 Featured Publication OBJECTIVE: Inflammation appears intricately linked to vein graft arterialization. We have previously shown that tumor necrosis factor (TNF) receptor-1 (TNFR1, p55) signaling augments vein graft neointimal hyperplasia (NH) and remodeling through its effects ... Full text Link to item Cite

Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis.

Journal article Arterioscler Thromb Vasc Biol · May 2007 Featured Publication OBJECTIVE: Mechanisms by which tumor necrosis factor-alpha (TNF) contributes to atherosclerosis remain largely obscure. We therefore sought to determine the role of the arterial wall TNF receptor-1 (TNFR1) in atherogenesis. METHODS AND RESULTS: Carotid art ... Full text Link to item Cite

Regulation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2.

Journal article J Biol Chem · December 8, 2006 Featured Publication Smooth muscle cell (SMC) proliferation and migration are substantially controlled by the platelet-derived growth factor receptor-beta (PDGFRbeta), which can be regulated by the Ser/Thr kinase G protein-coupled receptor kinase-2 (GRK2). In mouse aortic SMCs ... Full text Link to item Cite

The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2. A mechanism for feedback inhibition.

Journal article J Biol Chem · September 2, 2005 Featured Publication G protein-coupled receptor kinase-2 (GRK2) serine-phosphorylates the platelet-derived growth factor receptor-beta (PDGFRbeta), and thereby diminishes signaling by the receptor. Because activation of GRK2 may involve phosphorylation of its N-terminal tyrosi ... Full text Link to item Cite

Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms.

Journal article Cardiovasc Res · February 15, 2005 Featured Publication OBJECTIVE: Because tumor necrosis factor-alpha (TNF) has been implicated in the pathogenesis of vein graft neointimal hyperplasia, we sought to determine mechanisms by which TNF could induce proliferative and migratory responses in smooth muscle cells (SMC ... Full text Link to item Cite

Vein graft neointimal hyperplasia is exacerbated by tumor necrosis factor receptor-1 signaling in graft-intrinsic cells.

Journal article Arterioscler Thromb Vasc Biol · December 2004 Featured Publication OBJECTIVE: Vein graft remodeling and neointimal hyperplasia involve inflammation, graft-intrinsic cells, and recruitment of vascular progenitor cells. We sought to examine if the inflammatory cytokine tumor necrosis factor (TNF) affects vein graft remodeli ... Full text Link to item Cite

Phosphorylation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na(+)/H(+) exchanger regulatory factor.

Journal article J Biol Chem · October 1, 2004 Featured Publication G protein-coupled receptor kinase-2 (GRK2) can phosphorylate and desensitize the platelet-derived growth factor receptor-beta (PDGFRbeta) in heterologous cellular systems. To determine whether GRK2 regulates the PDGFRbeta in physiologic systems, we examine ... Full text Link to item Cite

Graft-extrinsic cells predominate in vein graft arterialization.

Journal article Arterioscler Thromb Vasc Biol · March 2004 Featured Publication OBJECTIVE: Vein graft disease involves neointimal smooth muscle cells, the origins of which are unclear. This study sought to characterize and quantitate vein graft infiltration by cells extrinsic to the graft in a mouse model of vein graft disease. METHOD ... Full text Link to item Cite

The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor.

Journal article J Biol Chem · November 7, 2003 Featured Publication Endocytosis of the low density lipoprotein (LDL) receptor (LDLR) in coated pits employs the clathrin adaptor protein ARH. Similarly, agonist-dependent endocytosis of heptahelical receptors in coated pits employs the clathrin adaptor beta-arrestin proteins. ... Full text Link to item Cite

Phosphorylation of the platelet-derived growth factor receptor-beta and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization.

Journal article J Biol Chem · December 13, 2002 Featured Publication Accumulating evidence suggests that receptor protein-tyrosine kinases, like the platelet-derived growth factor receptor-beta (PDGFRbeta) and epidermal growth factor receptor (EGFR), may be desensitized by serine/threonine kinases. One such kinase, G protei ... Full text Link to item Cite

Neointimal hyperplasia rapidly reaches steady state in a novel murine vein graft model.

Journal article J Vasc Surg · October 2002 Featured Publication OBJECTIVE: Neointimal hyperplasia remains a principal cause of vein graft failure. Genetic contributions to vein graft neointimal hyperplasia could be well studied in the mouse; however, surgical approaches to vein bypass surgery in the mouse have yet to r ... Link to item Cite

Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells reduces neointimal hyperplasia.

Journal article J Mol Cell Cardiol · October 2002 Featured Publication The activation of vascular smooth muscle cells (SMCs) in neointimal hyperplasia involves signaling through receptor tyrosine kinases as well as G protein-coupled receptors. Overexpression of G protein-coupled receptor kinase-2 (GRK2) in SMCs can attenuate ... Full text Link to item Cite

Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells attenuates mitogenic signaling via G protein-coupled and platelet-derived growth factor receptors.

Journal article Circulation · August 15, 2000 Featured Publication BACKGROUND: Neointimal hyperplasia involves activation of smooth muscle cells (SMCs) by several G protein-coupled receptor (GPCR) agonists, including endothelin-1, angiotensin II, thrombin, and thromboxane A(2). Signaling of many GPCRs is diminished by GPC ... Full text Link to item Cite