David Lominadze, Ph.D.

David Lominadze, Ph.D.

DAVID LOMINADZE, Ph.D.
dglomi01@louisville.edu
Professor
Institute of Physiology, Tbilisi, Georgia, 1990

Our goal is to understand mechanisms of microcirculatory disorders during various cardiovascular and cerebrovascular diseases. We study mechanisms of blood cell interactions with each other and with vascular endothelium and blood plasma components. Changes in these interactions are involved in microvascular permeability, angiogenesis, and vascular remodeling affecting normal healing process during pathologies such as hypertension, diabetes, stroke, traumatic brain injury, and Alzheimer’s disease.

Presently we study role of vascular dysfunction in neuronal degeneration. We are focused on mechanisms of caveolar protein transcytosis during traumatic brain injury or hyperhomocysteinemia. Changes in cerebrovascular permeability to proteins lead to vascular remodeling and fibrotic plaque formations similar to those seen in Alzheimer’s disease. They also affect endothelial-astrocyte coupling mechanism and result in neuronal degeneration leading to an altered cognition.

Mouse model of traumatic brain injury is used. Changes in microvascular permeability are studied by intravital fluorescence microscopy. We also use a model of isolated and perfused microvessels. Some specific mechanisms are studied in cell culture and/or observed in situ using immunohistochemistry and confocal microscopy analyses. In addition, we use various biochemical and molecular biology methods. Changes in memory are tested with several methods (e.g. novel object recognition test and Y-maze test).

Selected Publications:

  1. Muradashvili N, Benton RL, Saatman K, Tyagi SC, Lominadze D. Ablation of matrix metalloproteinase-9 gene decreases cerebrovascular permeability and fibrinogen deposition post traumatic brain injury in mice. Special issue entitled: “Mechanisms and therapies for acute CNS insults”. (Ed. Raghu Vemuganti). Metabolic Brain Disease. 2015; 30(2): 411-426. http://www.ncbi.nlm.nih.gov/pubmed/24771110
  2. Muradashvili N, Tyagi R, Metreveli N, Tyagi SC, Lominadze D. Ablation of MMP-9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia. J Cerebral Blood Flow and Metabolism. 2014; 34(9):1472-1482. (DL and TSC are equally contributed senior authors) http://www.ncbi.nlm.nih.gov/pubmed/24865997
  3. Muradashvili N, Khundmiri SJ, Tyagi R, Gartung A, Dean WL, Lee M-J, Lominadze D. Sphingolipids affect fibrinogen-induced caveolar transcytosis and cerebrovascular permeability. Am. J. Physiol. Cell Physiol. 2014; 307(2): C169-C179. http://www.ncbi.nlm.nih.gov/pubmed/24829496
  4. Muradashvili N, Lominadze D.      Role of fibrinogen in cerebrovascular dysfunction after traumatic brain injury. Brain Injury. 2013; 27(13-14): 1508-1515. http://www.ncbi.nlm.nih.gov/pubmed/24063686
  5. Muradashvili N, Tyagi R, Lominadze D.  A dual-tracer method for differentiating transendothelial transport from paracellular leakage in vivo and in vitro. Frontiers in Vascular Physiology. 2012; 3: 166-172.     Featured on Antibody Resource http://www.frontiersin.org/Journal/Abstract.aspx?s=1141&name=vascular_physiology&ART_DOI=10.3389/fphys.2012.00166 http://www.ncbi.nlm.nih.gov/pubmed/22754530
  6. Muradashvili N,  Qipshidze N, Munjal C, Givvimani S. Benton R, Tyagi, SC, Lominadze D. Fibrinogen-induced increased pial venular permeability in mice. J Cerebral Blood Flow and Metabolism. 2012; 32(1): 150-163. Cover photo. http://www.ncbi.nlm.nih.gov/pubmed/21989482
  7. Muradashvili N, Tyagi N, Tyagi R, Munjal C, Lominadze D. Fibrinogen alters mouse brain endothelial cell layer integrity affecting vascular endothelial cadherin. Biochemical and Biophysical Research Communications. 2011; 413(4): 509-514. http://www.ncbi.nlm.nih.gov/pubmed/21920349
  8. Lominadze D, Dean WL, Tyagi SC, Roberts AM. Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease. Acta Physiologica. 2010; 198(1): 1-13. http://www.ncbi.nlm.nih.gov/pubmed/19723026
  9. Sen U, Tyagi N, Patibandla PK, Dean WL, Tyagi SC, Roberts AM, Lominadze D. Fibrinogen-induced production of endothelin-1 from endothelial cells. American Journal of Physiology - Cell Physiology. 2009; 296(4): C840-C847. http://www.ncbi.nlm.nih.gov/pubmed/19193866
  10. Tyagi N, Roberts AM, Dean WL, Tyagi SC, Lominadze D. Fibrinogen induces endothelial cell permeability.  Molecular and Cellular Biochemistry. 2008; 307(1-2):13-22. http://www.ncbi.nlm.nih.gov/pubmed/17849175
  11. Tyagi N, Moshal KS, Tyagi SC, Lominadze D. GABAA receptor mitigates homocysteine-induced endothelial cell permeability. Endothelium. 2007; 14(6): 315-323.  http://www.ncbi.nlm.nih.gov/pubmed/18080868
  12. Lominadze D, Roberts AM, Tyagi N, Tyagi SC. Homocysteine causes cerebrovascular leakage in mice. American Journal of Physiology, Heart and Circulatory Physiology. 2006; 290: H1206-H1213.  http://www.ncbi.nlm.nih.gov/pubmed/16258031
  13. Lominadze D, Tsakadze N, Sen U, Falcone JC, D’Souza SE. Fibrinogen- and its fragment D-induced vascular constriction. American Journal of Physiology, Heart and Circulatory Physiology. 2005; 288(3): H1257--H1264.  http://www.ncbi.nlm.nih.gov/pubmed/15739255
  14. Lominadze D, Dean WL. Involvement of fibrinogen specific binding in erythrocyte aggregation. FEBS Letters. 2002; 517(1-3): 41-44. http://www.ncbi.nlm.nih.gov/pubmed/1206240
  15. Lominadze D, Joshua IG, Schuschke DA. Increased erythrocyte aggregation in spontaneously hypertensive rats. American Journal of Hypertension. 1998; 11(7): 784-789.  http://www.ncbi.nlm.nih.gov/pubmed/9683038
  16. Lominadze D, Joshua IG, Schuschke DA. In vivo platelet thrombus formation in microvessels of spontaneously hypertensive rats. American Journal of Hypertension. 1997; 10(10): 1140-1146. http://www.ncbi.nlm.nih.gov/pubmed/9370385