Description of Research
Link to lab page
Our overall research interest is to understand the cellular mechanisms that regulate permeability in intact microvessels.

Our research is mainly focused on the investigation of signaling mechanisms of permeability modulation in intact microvessels. Our current research involves the study of signaling pathways that regulate leukocyte-endothelium interactions, the expression of adhesion molecules on endothelial cells and the associated changes in permeability in intact microvessels.

Single microvessel perfusion is the basic technique employed in our laboratory. Changes in microvessel permeability will be determined by paired measurements of hydraulic conductivity, Lp, or solute permeability coefficient before and after leukocyte adhesion, migration and/or exposure to inflammatory mediators in the same microvessel. We have established methods that combine single microvessel perfusion with fluorescence microscopy and confocal microscopy. The combined methods allow us to directly evaluate the relationship between changes in ion concentration, such as [Ca2+]i in endothelial cells, and the changes in permeability. It also will allow us to conduct fluorescence immuno-staining to illustrate the spatial distribution of adhesion molecules in live microvessels.

Research Support
Ongoing:

• NIH/NHLBI  RO1 HL-56237 (Pingnian He, Principal Investigator)

Title: "Cellular Modulation of Microvessel Permeability in vivo".
  
The overall aims of this project are to investigate the signal transduction pathways in the regulation of microvessel permeability.  The specific project for current funding cycle is to investigate the role of platelets in the blood cell aggregation and aggregate adhesion-induced increases in microvessel permeability. 

• NIH/NHLBI  RO1 HL-084338 (Pingnian He, Principal Investigator)

Title: "Nitric Oxide and Microvessel Permeability in vivo".  
   
This project aims to investigate the role of nitric oxide in the regulation of microvessel permeability during acute inflammatory conditions. 

• NSF/WVPSCoR  (P.I: Dan C. Flynn, Mentor: Pingnian He), Training grant. “Cancer Nanotechnology Training program”.

Recent Publications

2008 Three-dimensional localization and quantification of PAF-induced gap
formation in intact venular microvessels

2002   Zeng, M, H. Zhang, C. Lowell, and P. He. Tumor necrosis factor-alpha-induced leukocyte adhesion and microvessel permeability. Am. J. Physiol. Heart and Circ Physiol 283: H2420-2430. Published on Aug. 8, 2002 as DOI 10.1152/ajpheart.00787.2001.

2004   Zhu, L, Schwegler-Berry D, Castranova V, and He P.  Internalization of caveolin-1 scaffolding domain facilitated by Antennapedia homeodomain attenuates PAF-induced increase in microvessel permeability.  Am J Physiol, Heart and Circ Physiol. 286: H195-H201.
  
2005   Bernatchez PN, Bauer PM, Yu J, Prendergast JS, He P, Sessa WC. Dissecting the molecular control of endothelial NO synthase by caveolin-1 using cell-permeable peptides.  Proc Natl Acad Sci U S A. 102: 761-766. 

2005   Minnear, F., L. Zhu, and P. He.  Sphingosine 1-phosphate prevents platelet activating factor-induced increase in hydraulic conductivity in mesenteric venules: pertussis toxin-sensitive.  Am J Physiol, Heart and Circ Physiol 289: H840-H844.

2005   Zhu, L and He P. Platelet activating factor increases endothelial [Ca2+]i and nitric oxide production in individually perfused intact microvessels. Am J Physiol, Heart and Circ Physiol 288: H2869-H2877.

2005   Zhu, L, Castranova V, and P He.  FMLP-stimulated neutrophils increase endothelial [Ca2+]i and microvessel permeability in the absence of adhesion: Role of reactive oxygen species.  Am. J. Physiol.Heart and Circ Physiol. 288: H1331-H1338.

2006   Zhu, L and He P. FMLP-Stimulated Release of Reactive Oxygen Species from TNF-a-Induced Adherent Leukocytes Increases Microvessel Permeability.  Am J Physiol, Heart and Circ Physiol. 290: H365-H372.

2006   He, P, Zhang H, Zhu L. and Jiang Y, Zhou, X. Leukocyte/Platelet Aggregate Adhesion and Vascular Permeability: Role of Activated Endothelial Cells. Am J Physiol, Heart and Circ Physiol. 291: H591-H599.