Genetic background of endothelial cell pathopyhsiology in pulmonary hypertension.

• Applicant: Dr. Nils Nickel
• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217553304

• Final Report Year: 2015

Final Report Abstract

This report shows the efficacy of elafin, a naturally occurring elastase inhibitor, in reversing severe experimentally-induced pulmonary hypertension associated with an obliterative vasculopathy, and in causing regression of the neointima in cultured explants of human pulmonary arteries taken from patients with pulmonary arterial hypertension. The mechanism involves elastase inhibition and caveolin-dependent amplification of BMPR2 signaling which together promote regression of occlusive lesions, endothelial restoration and vascular regeneration.

Publications

• American Thoracic Society Meeting 2014, San Diego, CA (USA). The Human Neutrophil Elastase Inhibitor Elafin Interacts With Caveolin- 1 To Facilitate BMPR-2 Signaling And Endothelial Homeostasis Associated With Reversal Of Experimental Pulmonary Hypertension
  NP. Nickel, M. Kaschwich, E. Spiekerkoetter, L. Wang, C. Li, K. Kim, H. Li, M. Rabinovitch
  
• American Thoracic Society Meeting 2013, Philadelphia, PN (USA). Elafin To Reverse Pulmonary Arterial Hypertension
  NP. Nickel, M. Kaschwich, E. Spiekerkoetter, L. Wang, C. Li, K. Kim, H. Li, M. Rabinovitch
  
• Stanford University Cardiovascular Institute Annual Retreat 2013, Stanford (CA). Elafin reverses pulmonary arterial hypertension and restores endothelial cell homeostasis
  NP. Nickel, M. Kaschwich, I. Diebold, G. Li, M. Rabinovitch