Christopher D. Kontos, MD

Department / Division:
Medicine / Cardiology

Address:
DUMC 3629
Durham, NC 27710

Appointment Telephone:
919-681-5816

Office Telephone:
919-684-2119

Fax Telephone:
919-684-8591

• MD, Medical College of Virginia (Virginia Commonwealth University School of Medicine), 1989

• Medicine, Medical College of Virginia, 1989-1993
• Cardiology, Duke University Medical Center, 1993-1997

Clinical Interests:
General cardiology

Research Interests:
The Kontos Lab studies the molecular mechanisms of angiogenesis and vascular remodeling. Studies are directed toward understanding how signal transduction by endothelial receptor tyrosine kinase (RTKs) regulates vascular growth in both physiological and pathological processes, including exercise, peripheral artery disease (PAD), atherosclerosis, and cancer.

Current projects include:

1. Signal transduction, mechanisms of activation, and downregulation of endothelial RTKs (mainly Tie1, Tie2, VEGFR-1, and VEGFR-2)

2. Differential effects of the Angiopoietins

3. Role of the inositol phosphatase PTEN in the regulation of vascular cell growth and remodeling

4. PTEN gene therapy for prevention of vein graft disease

5. Angiogenic signaling in skeletal muscle, including mechanisms of exercise-induced angiogenesis

6. Proteolytic cleavage and shedding of endothelial RTKs

7. Angiogenic proteins as biomarkers in peripheral artery disease

Representative Publications:
Ahmed A, Fujisawa T, Niu XL, Ahmad S, Al-Ani B, Chudasama K, Abbas A, Potluri R, Bhandari V, Findley CM, Lam GK, Huang J, Hewett PW, Cudmore M, Kontos CD. Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide. Circ Res. 2009 Jun 19;104(12):1333-6. (2009) Abstract

Xie D, Findley CM, Greenfield JM, Pippen AM, Kontos CD, Donatucci CF, Annex BH. A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med. 2008 Sep;5(9):2069-78. (2008) Abstract

White RR, Roy JA, Viles KD, Sullenger BA, Kontos CD. A nuclease-resistant RNA aptamer specifically inhibits angiopoietin-1-mediated Tie2 activation and function. Angiogenesis. 2008;11(4):395-401. (2008) Abstract

Findley CM, Mitchell RG, Duscha BD, Annex BH, Kontos CD. Plasma levels of soluble Tie2 and vascular endothelial growth factor distinguish critical limb ischemia from intermittent claudication in patients with peripheral arterial disease. J Am Coll Cardiol. 2008 Jul 29;52(5):387-93. (2008) Abstract

Li Y, Hazarika S, Xie D, Pippen AM, Kontos CD, Annex BH. 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. Diabetes. 2007 Mar;56(3):656-65. (2007) Abstract

Kontos CD, Annex BH. Engineered transcription factors for therapeutic angiogenesis. Curr Opin Mol Ther. 2007 Apr;9(2):145-52. (2007) Abstract

Hazarika S, Dokun AO, Li Y, Popel AS, Kontos CD, Annex BH. 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. Circ Res. 2007 Oct 26;101(9):948-56. (2007) Abstract

Findley CM, Cudmore MJ, Ahmed A, Kontos CD. VEGF induces Tie2 shedding via a phosphoinositide 3-kinase/Akt dependent pathway to modulate Tie2 signaling. Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2619-26. (2007) Abstract

Xie D, Li Y, Reed EA, Odronic SI, Kontos CD, Annex BH. An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb ischemia. J Vasc Surg. 2006 Jul;44(1):166-75. (2006) Abstract

White ES, Atrasz RG, Hu B, Phan SH, Stambolic V, Mak TW, Hogaboam CM, Flaherty KR, Martinez FJ, Kontos CD, Toews GB. Negative regulation of myofibroblast differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on chromosome 10). Am J Respir Crit Care Med. 2006 Jan 1;173(1):112-21. (2006) Abstract

Liu S, Premont RT, Kontos CD, Zhu S, Rockey DC. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Nat Med. 2005 Sep;11(9):952-8. (2005) Abstract

Huang J, Niu XL, Pippen AM, Annex BH, Kontos CD. Adenovirus-mediated intraarterial delivery of PTEN inhibits neointimal hyperplasia. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):354-8. (2005) Abstract

Hata JA, Petrofski JA, Schroder JN, Williams ML, Timberlake SH, Pippen A, Corwin MT, Solan AK, Jakoi A, Gehrig TR, Kontos CD, Milano CA. Modulation of phosphatidylinositol 3-kinase signaling reduces intimal hyperplasia in aortocoronary saphenous vein grafts. J Thorac Cardiovasc Surg. 2005 Jun;129(6):1405-13. (2005) Abstract

Peters KG, Kontos CD, Lin PC, Wong AL, Rao P, Huang L, Dewhirst MW, Sankar S. Functional significance of Tie2 signaling in the adult vasculature. Recent Prog Horm Res. 2004;59:51-71. (2004) Abstract

Dai Q, Huang J, Klitzman B, Dong C, Goldschmidt-Clermont PJ, March KL, Rokovich J, Johnstone B, Rebar EJ, Spratt SK, Case CC, Kontos CD, Annex BH. Engineered zinc finger-activating vascular endothelial growth factor transcription factor plasmid DNA induces therapeutic angiogenesis in rabbits with hindlimb ischemia. Circulation. 2004 Oct 19;110(16):2467-75. (2004) Abstract

White RR, Shan S, Rusconi CP, Shetty G, Dewhirst MW, Kontos CD, Sullenger BA. Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5028-33. (2003) Abstract

Niu XL, Peters KG, Kontos CD. Deletion of the carboxyl terminus of Tie2 enhances kinase activity, signaling, and function. Evidence for an autoinhibitory mechanism. J Biol Chem. 2002 Aug 30;277(35):31768-73. (2002) Abstract

Kontos CD, Cha EH, York JD, Peters KG. The endothelial receptor tyrosine kinase Tie1 activates phosphatidylinositol 3-kinase and Akt to inhibit apoptosis. Mol Cell Biol. 2002 Mar;22(6):1704-13. (2002) Abstract

Huang J, Kontos CD. PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. J Biol Chem. 2002 Mar 29;277(13):10760-6. (2002) Abstract

Kontos CD, Stauffer TP, Yang WP, York JD, Huang L, Blanar MA, Meyer T, Peters KG. Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol. 1998 Jul;18(7):4131-40. (1998) Abstract