Christopher Dale Kontos

Journal article Circ Res · June 19, 2009 Featured Publication Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 ... Full text Link to item Cite

A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits.

Journal article J Sex Med · September 2008 Featured Publication INTRODUCTION: Hypercholesterolemia causes a decrease in normal corporal tissue vasoreactivity in a preclinical model of erectile dysfunction. Previous studies have shown that intracorporal injection (ICI) of basic fibroblast growth factor (bFGF) reverses s ... Full text Link to item Cite

Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease.

Journal article J Am Coll Cardiol · July 29, 2008 Featured Publication OBJECTIVES: Our purpose was to determine whether factors that regulate angiogenesis are altered in peripheral arterial disease (PAD) and whether these factors are associated with the severity of PAD. BACKGROUND: Alterations in angiogenic growth factors occ ... Full text Link to item Cite

A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function.

Journal article Angiogenesis · 2008 Featured Publication Tie2 is a receptor tyrosine kinase that is expressed predominantly in the endothelium and plays key roles in both physiological and pathological angiogenesis. The ligands for Tie2, the angiopoietins (Ang), perform opposing functions in vascular maintenance ... Full text Link to item Cite

VEGF induces Tie2 shedding via a phosphoinositide 3-kinase/Akt dependent pathway to modulate Tie2 signaling.

Journal article Arterioscler Thromb Vasc Biol · December 2007 Featured Publication OBJECTIVE: Tie2 and its ligands, the angiopoietins (Ang), are required for embryonic and postnatal angiogenesis. Previous studies have demonstrated that Tie2 is proteolytically cleaved, resulting in the production of a 75-kDa soluble receptor fragment (sTi ... Full text Link to item Cite

Impaired angiogenesis after hindlimb ischemia in type 2 diabetes mellitus: differential regulation of vascular endothelial growth factor receptor 1 and soluble vascular endothelial growth factor receptor 1.

Journal article Circ Res · October 26, 2007 Featured Publication Deficient angiogenesis after ischemia may contribute to worse outcomes of peripheral arterial disease in patients with diabetes mellitus (DM). Vascular endothelial growth factor (VEGF) and its receptors promote angiogenesis. We hypothesized that in periphe ... Full text Link to item Cite

Engineered transcription factors for therapeutic angiogenesis.

Journal article Curr Opin Mol Ther · April 2007 Featured Publication Angiogenesis is defined as the growth and proliferation of blood vessels from existing vascular structures. Therapeutic angiogenesis seeks to harness the mechanisms of vascular growth to treat disorders of inadequate tissue perfusion. Early clinical trials ... Link to item Cite

In mice with type 2 diabetes, a vascular endothelial growth factor (VEGF)-activating transcription factor modulates VEGF signaling and induces therapeutic angiogenesis after hindlimb ischemia.

Journal article Diabetes · March 2007 Featured Publication Peripheral arterial disease is a major complication of diabetes. The ability to promote therapeutic angiogenesis may be limited in diabetes. Type 2 diabetes was induced by high-fat feeding C57BL/6 mice (n = 60). Normal chow-fed mice (n = 20) had no diabete ... Full text Link to item Cite

An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb ischemia.

Journal article J Vasc Surg · July 2006 Featured Publication OBJECTIVE: Angiogenesis is the growth and proliferation of blood vessels from existing vascular structures, and therapeutic angiogenesis seeks to promote blood vessel growth to improve tissue perfusion. Vascular endothelial growth factor (VEGF) is a protot ... Full text Link to item Cite

Negative regulation of myofibroblast differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on chromosome 10).

Journal article Am J Respir Crit Care Med · January 1, 2006 Featured Publication RATIONALE: Myofibroblasts are primary effector cells in idiopathic pulmonary fibrosis (IPF). Defining mechanisms of myofibroblast differentiation may be critical to the development of novel therapeutic agents. OBJECTIVE: To show that myofibroblast differen ... Full text Link to item Cite

A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension.

Journal article Nat Med · September 2005 Featured Publication Nitric oxide (NO) production by endothelial cell nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. We sought to understand the mechanism underlying defective eNOS fun ... Full text Link to item Cite

Modulation of phosphatidylinositol 3-kinase signaling reduces intimal hyperplasia in aortocoronary saphenous vein grafts.

Journal article J Thorac Cardiovasc Surg · June 2005 Featured Publication OBJECTIVES: Fifty percent of human aortocoronary saphenous vein grafts are occluded after 10 years. Intimal hyperplasia is an initial step in graft occlusion and consists of vascular smooth muscle cell proliferation. Phosphatidylinositol 3-kinase and its d ... Full text Link to item Cite

Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia.

Journal article Arterioscler Thromb Vasc Biol · February 2005 Featured Publication OBJECTIVE: Phosphoinositide (PI) 3-kinase promotes vascular smooth muscle cell (VSMC) responses necessary for neointimal hyperplasia. We recently demonstrated that the inositol 3-phosphatase PTEN is expressed in VSMCs and that its overexpression inhibits t ... Full text Link to item Cite

Engineered zinc finger-activating vascular endothelial growth factor transcription factor plasmid DNA induces therapeutic angiogenesis in rabbits with hindlimb ischemia.

Journal article Circulation · October 19, 2004 Featured Publication BACKGROUND: Therapeutic angiogenesis seeks to promote blood vessel growth to improve tissue perfusion. Vascular endothelial growth factor (VEGF) exists in multiple isoforms. We investigated an engineered zinc finger-containing transcription factor plasmid ... Full text Link to item Cite

Functional significance of Tie2 signaling in the adult vasculature.

Journal article Recent Prog Horm Res · 2004 Featured Publication Abundant data now demonstrate that the growth of new blood vessels, termed angiogenesis, plays both pathological and beneficial roles in human disease. Based on these data, a tremendous effort has been undertaken to understand the molecular mechanisms that ... Full text Link to item Cite

Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.

Journal article Proc Natl Acad Sci U S A · April 29, 2003 Featured Publication Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangi ... Full text Link to item Cite

Deletion of the carboxyl terminus of Tie2 enhances kinase activity, signaling, and function. Evidence for an autoinhibitory mechanism.

Journal article J Biol Chem · August 30, 2002 Featured Publication Tie2 is an endothelial receptor tyrosine kinase that is required for both embryonic vascular development and tumor angiogenesis. There is considerable interest in understanding the mechanisms of Tie2 activation for therapeutic purposes. The recent solution ... Full text Link to item Cite

PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects.

Journal article J Biol Chem · March 29, 2002 Featured Publication Phosphatidylinositol 3-kinase is activated by vascular endothelial growth factor (VEGF), and many of the angiogenic cellular responses of VEGF are regulated by the lipid products of phosphatidylinositol 3-kinase. The tumor suppressor PTEN has been shown to ... Full text Link to item Cite

The endothelial receptor tyrosine kinase Tie1 activates phosphatidylinositol 3-kinase and Akt to inhibit apoptosis.

Journal article Mol Cell Biol · March 2002 Featured Publication Tie1 is an orphan receptor tyrosine kinase that is expressed almost exclusively in endothelial cells and that is required for normal embryonic vascular development. Genetic studies suggest that Tie1 promotes endothelial cell survival, but other studies hav ... Full text Link to item Cite

Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.

Journal article Mol Cell Biol · July 1998 Featured Publication Tie2 is an endothelium-specific receptor tyrosine kinase that is required for both normal embryonic vascular development and tumor angiogenesis and is thought to play a role in vascular maintenance. However, the signaling pathways responsible for the funct ... Full text Link to item Cite