Endothelial cell activation by hemodynamic shear stress derived from arteriovenous fistula for hemodialysis access.
Intimal hyperplasia (IH) is the first cause of failure of an arteriovenous fistula (AVF). The aim of the present study was to investigate the effects on endothelial cells (ECs) of shear stress waveforms derived from AVF areas prone to develop IH. We used a cone-and-plate device to obtain real-time control of shear stress acting on EC cultures. We exposed human umbilical vein ECs for 48 h to different shear stimulations calculated in a side-to-end AVF model. Pulsatile unidirectional flow, representative of low-risk stenosis areas, induced alignment of ECs and actin fiber orientation with flow. Shear stress patterns of reciprocating flow, derived from high-risk stenosis areas, did not affect EC shape or cytoskeleton organization, which remained similar to static cultures. We also evaluated flow-induced EC expression of genes known to be involved in cytoskeletal remodeling and expression of cell adhesion molecules. Unidirectional flow induced a significant increase in Kruppel-like factor 2 mRNA expression, whereas it significantly reduced phospholipase D1, α4-integrin, and Ras p21 protein activator 1 mRNA expression. Reciprocating flow did not increase Kruppel-like factor 2 mRNA expression compared with static controls but significantly increased mRNA expression of phospholipase D1, α4-integrin, and Ras p21 protein activator 1. Reciprocating flow selectively increased monocyte chemoattractant protein-1 and IL-8 production. Furthermore, culture medium conditioned by ECs exposed to reciprocating flows selectively increased smooth muscle cell proliferation compared with unidirectional flow. Our results indicate that protective vascular effects induced in ECs by unidirectional pulsatile flow are not induced by reciprocating shear forces, suggesting a mechanism by which oscillating flow conditions may induce the development of IH in AVF and vascular access dysfunction.
Department of Biomedical Engineering, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy;
Marco
M
Franzoni
Department of Biomedical Engineering, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy;
Irene
I
Cattaneo
Department of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri, Be rgamo, Italy; and.
Lorena
L
Longaretti
Department of Biomedical Engineering, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy;
Marina
M
Figliuzzi
Department of Biomedical Engineering, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy;
Bogdan
B
Ene-Iordache
Department of Biomedical Engineering, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy; Department of Management, Information and Production Engineering, University of Bergamo, Dalmine, Italy andrea.remuzzi@marionegri.it.
Andrea
A
Remuzzi
D008841:Actin Cytoskeleton / Q000378:metabolism; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006439:Hemodynamics; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D040542:Mechanotransduction, Cellular; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000378:metabolism; D006435:Renal Dialysis; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors
D017077:Culture Media, Conditioned; D016207:Cytokines; D012333:RNA, Messenger
arteriovenous fistula; endothelial cells; hemodialysis; intimal hyperplasia; wall shears stress