Temporal gradient in shear but not steady shear stress induces PDGF-A and MCP-1 expression in endothelial cells: role of NO, NF kappa B, and egr-1.

Three well-defined laminar flow profiles were created to distinguish the influence of a gradient in shear and steady shear on platelet-derived growth factor A (PDGF-A) and monocyte chemoattractant protein-1 (MCP-1) expression in human endothelial cells. The flow profiles (16 dyne/cm2 maximum shear stress) were ramp flow (shear stress smoothly transited at flow onset), step flow (shear stress abruptly applied at flow onset), and impulse flow (shear stress abruptly applied for 3 s only). Ramp flow induced only minor expression of PDGF-A and did not increase MCP-1 expression. Step flow increased PDGF-A and MCP-1 mRNA levels 3- and 2-fold at 1.5 hours, respectively, relative to ramp flow. In contrast, impulse flow increased PDGF-A and MCP-1 expression 6- and 7-fold at 1.5 hours, and these high levels were sustained for at least 4 hours. These results indicate that a temporal gradient in shear (impulse flow and the onset of step flow) and steady shear (ramp flow and the steady component of step flow) stimulates and diminishes the expression of PDGF-A and MCP-1, respectively. NO synthase inhibitor NG-amino-L-arginine (L-NAA) was found to markedly enhance MCP-1 and PDGF-A expression induced by step flow, but decrease their expression induced by impulse flow, in a dose-dependent manner. NO donor spermine-NONOate (SPR/NO) dose-dependently reduced the MCP-1 and PDGF-A expression induced by impulse flow. Moreover, impulse flow was found to stimulate sustained (4 hours) I kappa B-alpha degradation and egr-1 mRNA induction. L-NAA prevented I kappa B-alpha degradation, whereas SPR/NO increased I kappa B-alpha resynthesis 2 hours after impulse flow. Both L-NAA and SPR/NO inhibited the impulse flow inducibility of egr-1 4 hours after the flow stimulation. The results show that both NO induced by steady shear and NO donor inhibit temporal gradient in shear-induced MCP-1 and PDGF-A expression by downregulation of their respective transcription factors NF kappa B and egr-1, whereas NO induced by impulse flow stimulates MCP-1 and PDGF-A expression by upregulation of the transcription factors. The above findings suggest distinct roles of temporal gradient in shear and steady shear in atherogenesis in vivo.

[1]  G. Natoli,et al.  Reactive Oxygen Intermediates (ROIs) Are Involved in the Intracellular Transduction of Angiotensin II Signal in C2C12 Cells , 1995, Annals of the New York Academy of Sciences.

[2]  J. Meinkoth,et al.  Nitric oxide and cGMP analogs activate transcription from AP‐1‐responsive promoters in mammalian cells , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  J S Beckman,et al.  Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. , 1996, The American journal of physiology.

[4]  G. Enikolopov,et al.  Amplification of calcium-induced gene transcription by nitric oxide in neuronal cells , 1993, Nature.

[5]  A. J. Valente,et al.  Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Kathleen M. Smith,et al.  Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. , 1988, The Journal of clinical investigation.

[7]  Jiahuai Han,et al.  The cis-acting phorbol ester "12-O-tetradecanoylphorbol 13-acetate"-responsive element is involved in shear stress-induced monocyte chemotactic protein 1 gene expression. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[8]  T. Collins,et al.  Egr-1 is activated in endothelial cells exposed to fluid shear stress and interacts with a novel shear-stress-response element in the PDGF A-chain promoter. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[9]  A. Tsai,et al.  Mutation of Glu-361 in Human Endothelial Nitric-oxide Synthase Selectively Abolishes L-Arginine Binding without Perturbing the Behavior of Heme and Other Redox Centers* , 1997, The Journal of Biological Chemistry.

[10]  S. Abramson,et al.  Outside-in signaling in the chondrocyte. Nitric oxide disrupts fibronectin-induced assembly of a subplasmalemmal actin/rho A/focal adhesion kinase signaling complex. , 1997, The Journal of clinical investigation.

[11]  L V McIntire,et al.  Flow effects on prostacyclin production by cultured human endothelial cells. , 1985, Science.

[12]  Y. Shyy,et al.  Cyclic strain-induced monocyte chemotactic protein-1 gene expression in endothelial cells involves reactive oxygen species activation of activator protein 1. , 1997, Circulation research.

[13]  J A Frangos,et al.  Shear stress increases endothelial platelet-derived growth factor mRNA levels. , 1991, The American journal of physiology.

[14]  M. Karin,et al.  The Ras-JNK pathway is involved in shear-induced gene expression , 1996, Molecular and cellular biology.

[15]  E. Werner,et al.  Characterization of bovine endothelial nitric oxide synthase as a homodimer with down-regulated uncoupled NADPH oxidase activity: tetrahydrobiopterin binding kinetics and role of haem in dimerization. , 1997, The Biochemical journal.

[16]  J. Zwiller,et al.  Stimulation of the Cyclic GMP Pathway by NO Induces Expression of the Immediate Early Genes c‐fos and junB in PC12 Cells , 1994, Journal of neurochemistry.

[17]  J. Ando,et al.  Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression. , 1994, The American journal of physiology.

[18]  K. O. Mercurius,et al.  Stimulation of transcription factors NF kappa B and AP1 in endothelial cells subjected to shear stress. , 1994, Biochemical and biophysical research communications.

[19]  J. Cornhill,et al.  Localization of atherosclerotic lesions in the human basilar artery. , 1980, Atherosclerosis.

[20]  M. Rekhter,et al.  Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? , 1994, Circulation research.

[21]  E. Moore,et al.  Nitric oxide reduces endothelial expression of intercellular adhesion molecule (ICAM)-1. , 1996, The Journal of surgical research.

[22]  H. Hsieh,et al.  Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear‐induced c‐fos expression , 1998, Journal of cellular physiology.

[23]  B L Langille,et al.  Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. , 1986, Science.

[24]  J A Frangos,et al.  Steady shear and step changes in shear stimulate endothelium via independent mechanisms--superposition of transient and sustained nitric oxide production. , 1996, Biochemical and biophysical research communications.

[25]  M. Ojha.  Wall shear stress temporal gradient and anastomotic intimal hyperplasia. , 1994, Circulation research.

[26]  J. Shyy,et al.  Reactive oxygen species are involved in shear stress-induced intercellular adhesion molecule-1 expression in endothelial cells. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[27]  M. Kuchan,et al.  Shear stress regulates endothelin-1 release via protein kinase C and cGMP in cultured endothelial cells. , 1993, The American journal of physiology.

[28]  M. Gimbrone,et al.  Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S Chien,et al.  Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[30]  C Kleinstreuer,et al.  Flow input waveform effects on the temporal and spatial wall shear stress gradients in a femoral graft-artery connector. , 1996, Journal of biomechanical engineering.

[31]  S. Ohno,et al.  NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. , 1994, Journal of immunology.

[32]  T. Karino,et al.  Flow patterns and spatial distribution of atherosclerotic lesions in human coronary arteries. , 1990, Circulation research.

[33]  T. Collins,et al.  Nuclear factor-kappa B interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. , 1995, The Journal of clinical investigation.

[34]  A. M. Lefer,et al.  Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. , 1997, The Journal of clinical investigation.

[35]  R. Busse,et al.  Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. , 1995, Circulation research.

[36]  J. Zweier,et al.  Mitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts , 1997, Science.

[37]  D. Harrison,et al.  Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Eddy,et al.  cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines , 1986, Nature.

[39]  F. Pileggi,et al.  Vascular free radical release. Ex vivo and in vivo evidence for a flow-dependent endothelial mechanism. , 1994, Circulation research.

[40]  K. Zitnay,et al.  Loss of Selective Endothelial Cell Vasoactive Functions Caused by Hypercholesterolemia in Pig Coronary Arteries , 1988, Circulation research.

[41]  John A. Frangos,et al.  Physical forces and the mammalian cell , 1993 .

[42]  D. Ku,et al.  Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. , 1988, Archives of pathology & laboratory medicine.

[43]  M. Gimbrone,et al.  Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells. , 1984, The Journal of clinical investigation.

[44]  R. Busse,et al.  Platelet-derived growth factor-stimulated superoxide anion production modulates activation of transcription factor NF-kappaB and expression of monocyte chemoattractant protein 1 in human aortic smooth muscle cells. , 1997, Circulation.

[45]  P. Vanhoutte,et al.  Flow-induced release of endothelium-derived relaxing factor. , 1986, The American journal of physiology.

[46]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[47]  S. Lohmann,et al.  Regulation of Gene Expression by cGMP-dependent Protein Kinase , 1996, The Journal of Biological Chemistry.

[48]  Eileen D. Adamson,et al.  A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization , 1988, Cell.

[49]  R M Nerem,et al.  Hemodynamics and the vascular endothelium. , 1993, Journal of biomechanical engineering.

[50]  N. Resnick,et al.  Hemodynamic forces are complex regulators of endothelial gene expression , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  M. Kuchan,et al.  Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. , 1994, The American journal of physiology.

[52]  J. Liao,et al.  Inhibition of Endothelial Vascular Cell Adhesion Molecule-1 Expression by Nitric Oxide Involves the Induction and Nuclear Translocation of IκBα* , 1997, The Journal of Biological Chemistry.

[53]  S. Moncada,et al.  Endogenous nitric oxide: physiology, pathology and clinical relevance , 1991, European journal of clinical investigation.