Physiology & Biophysics

Curriculum Vita

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

Our research interests are: blood cell interactions and their adhesion to vascular endothelium, microvascular permeability, angiogenesis, and vascular remodeling during cardiovascular and cerebrovascular diseases. 

Changes in blood rheological properties result in severe complications during many cardiovascular diseases and cerebrovascular disorders. These pathologies are inevitably accompanied by increased content of plasma adhesion proteins (e.g. fibrinogen), enhanced platelet and leukocyte adhesion to the vascular wall, and increased erythrocyte aggregability and rigidity. These changes lead to alterations in blood rheological properties and cause further complications during cardiovascular diseases. Our goal is to study the mechanisms involved in blood cell interactions, platelet thrombogenesis, red blood cell aggregation, neutrophil activation and transendothelial migration, blood stasis, blood cell adhesion to vascular endothelium, endothelial activation, and vasoreactivity. Our recent studies show that increased blood content of fibrinogen enhances arterial constriction and is involved in regulated production of endothelin-1. Increase in blood content of fibrinogen leads to an increased macromolecular leakage in microvessels through enhanced formation of filamentous actin in endothelial cells and disruption of endothelial layer integrity. Mechanisms of these effects during various inflammatory diseases associated with increased blood fibrinogen content is the main focus of our recent investigation.

The experimental approaches used in our research include intravital microscopy (rats, mice), isolated and perfused microvessel methods, and cell culture. We combine these with various imaging techniques, including confocal microscopy and atomic force microscopy. In hemorheolgy studies, we use cone-and-plate type viscometer and flow chambers. Blood cell interactions are studied using a flow cytometry technique and confocal microscopy. In addition, biochemical and molecular analyses techniques including functional proteomics (two dimensional gel electrophoresis) are used to determine the role of plasma adhesion proteins, cellular adhesion molecules, and integrins in vascular inflammatory responses during pathologies such as hypertension, copper-deficiency, ischemia/reperfusion injury, and hyperhomocysteinemia.

Selected publications:

Lominadze D, Joshua IG, Schuschke DA. In vivo platelet thrombus formation in microvessels of spontaneously hypertensive rats. American J. Hypertension.
1997; 10(10): 1140-1146.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9370385&query_hl=1&itool=pubmed_docsum

Lominadze D, Joshua IG, Schuschke DA. Increased erythrocyte aggregation in spontaneously hypertensive rats. American J. Hypertension. 1998; 11(7): 784-789.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9683038&query_hl=1&itool=pubmed_docsum

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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12062406&itool=iconabstr&query_hl=1&itool=pubmed_docsum

Roberts AM. Ovechkin AV, Mowbray JG, Robinson TW, Lominadze D. Effects of pulmonary ischemia-reperfusion on platelet adhesion in subpleural arterioles in rabbits.  Microvascular Research. 2004; 67(1): 29-37.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14709400&itool=iconabstr&query_hl=1&itool=pubmed_docsum

Lominadze D, Saari JT, Percival SS, Schuschke DA. Proinflammatory effects of copper deficiency on neutrophils and lung endothelial cells. Immunology and Cell Biology. 2004; 82: 231-238.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15186252&itool=iconabstr&query_hl=1&itool=pubmed_docsum

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://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1http://ajpheart.physiology.org/cgi/content/abstract/00856.2004v1Lominadze 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://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206http://ajpheart.physiology.org/cgi/content/full/290/3/H1206

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.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/17849175?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

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.echo.louisville.edu/pubmed/19193866?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Tyagi N, Vacek TP, Sen U, Moshal KS, Tyagi SC, Lominadze D. Activation of GABA-A receptor ameliorates homocysteine-induced MMP-9 activation by ERK pathway. Journal of Cellular Physiology. 2009; 220(1): 257-266.
http://www.ncbi.nlm.nih.gov.echo.louisville.edu/pubmed/19308943?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Patibandla PK, Tyagi N, Dean WL, Tyagi SC, Roberts AM, Lominadze D. Fibrinogen induces alteration of endothelial cell tight junction proteins. Journal of Cellular Physiology. 2009; 221(1): 195-203.
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805018

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.pubmedcentral.gov/articlerender.fcgi?artid=2803614

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: 509-514.
http://www.ncbi.nlm.nih.gov/pubmed/21920349

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.
http://www.ncbi.nlm.nih.gov/pubmed/21989482http://www.ncbi.nlm.nih.gov/pubmed/21989482

Munjal C, Tyagi N, Lominadze D, Tyagi SC. Matrix metalloproteinase-9 in homocysteine-induced intestinal microvascular endothelial paracellular and transcellular permeability. Journal of Cellular Biochemistry. 2012; (in press; 2011 Nov 17. doi: 10.1002/jcb.23451. [Epub ahead of print]).  (DL and TSC are equally contributed senior authors).
http://www.ncbi.nlm.nih.gov/pubmed/22275073

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.
http://www.frontiersin.org/Journal/Abstract.aspx?s=1141&name=vascular_physiology&ART_DOI=10.3389/fphys.2012.00166