DOI: http://dx.doi.org/10.18203/issn.2454-2156.IntJSciRep20212391

Passage dependent changes in nuclear and cytoskeleton structures of endothelial cells under laminar shear stress or cyclic stretch

Yizhi Jiang, Nathaniel Witt, Julie Y. Ji

Abstract


Background: The ability of vascular endothelium to sense and respond to the mechanical stimuli generated by blood flow is pivotal in maintaining arterial homeostasis. A steady laminar flow tends to provide athero-protective effect via regulating endothelial functions, vascular tone, and further remodeling process. As arterial aging appeared to be an independent risk factor of cardiovascular diseases, it is critical to understand the effects of cell senescence on endothelial dysfunction under dynamic mechanical stimuli.

Methods: In this study, we investigated the morphological responses of aortic endothelial cells toward laminar flow or cyclic stretch. Automated image recognition methods were applied to analyze image data to avoid bias. Differential patterns of morphological adaptations toward distinct mechanical stimuli were observed, and the shear-induced changes were found to be more associated with cell passages than that of cyclic strain.  

Results: Our results demonstrated that the cytoskeleton and nuclear structural adaptations in endothelial cells toward laminar flow were altered over prolonged culture, suggesting that the failure of senescent endothelial cells to adapt to the applied shear stress morphologically could be one of the contributors to endothelial dysfunctions during vascular aging.

Conclusions: Results indicated that cells were able to adjust their cytoskeleton and nuclear alignment and nuclear shapes in response to the applied mechanical stimuli, and that the shear-induced changes were more dependent on PD levels, where cells with higher PDL were more responsive to external forces.


Keywords


Nucleus, Cytoskeleton, Shear stress, Cyclic stretch, Endothelial cells

Full Text:

PDF

References


Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):139-596.

Gimbrone MA, Garcia CG. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res. 2016;118(4):620-36.

Vasile E, Tomita Y, Brown LF, Kocher O, Dvorak HF. Differential expression of thymosin beta-10 by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sites of atherosclerosis. FASEB J. 2001;15(2):458-66.

Kumazaki T, Kobayashi M, Mitsui Y. Enhanced expression of fibronectin during in vivo cellular aging of human vascular endothelial cells and skin fibroblasts. Exp Cell Res. 1993;205(2):396-402.

Chung HY, Lee EK, Choi YJ, Kim JM, Kim DH, Zou Y, Kim CH, et al. Molecular inflammation as an underlying mechanism of the aging process and age-related diseases. J Dent Res. 2011;90(7):830-40.

Minamino T, Komuro I. Vascular cell senescence: contribution to atherosclerosis. Circ Res. 2007;100(1):15-26.

Brown AJ, Teng Z, Evans PC, Gillard JH, Samady H, Bennett MR. Role of biomechanical forces in the natural history of coronary atherosclerosis. Nat Rev Cardiol. 2016;13(4):210-20.

Vanderlaan PA, Reardon CA, Getz GS. Site specificity of atherosclerosis: site-selective responses to atherosclerotic modulators. Arterioscler Thromb Vasc Biol. 2004;24(1):12-22.

Liang Y, Zhu H, Friedman MH. The correspondence between coronary arterial wall strain and histology in a porcine model of atherosclerosis. Phys Med Biol. 2009;54(18):5625-41.

Popele NM, Grobbee DE, Bots ML, Asmar R, Topouchian J, Reneman RS, et al. Association between arterial stiffness and atherosclerosis: the Rotterdam Study. Stroke. 2001;32(2):454-60.

Moore JE, Xu C, Glagov S, Zarins CK, Ku DN. Fluid wall shear stress measurements in a model of the human abdominal aorta: oscillatory behavior and relationship to atherosclerosis. Atherosclerosis. 1994;110(2):225-40.

Ando J, Yamamoto K. Effects of shear stress and stretch on endothelial function. Antioxid Redox Signal. 2011;15(5):1389-403.

Nerem RM, Levesque MJ, Cornhill JF. Vascular endothelial morphology as an indicator of the pattern of blood flow. J Biomech Eng. 1981;103(3):172-6.

Langille BL, Adamson SL. Relationship between blood flow direction and endothelial cell orientation at arterial branch sites in rabbits and mice. Circ Res. 1981;48(4):481-8.

Flaherty JT, Pierce JE, Ferrans VJ, Patel DJ, Tucker WK, Fry DL. Endothelial nuclear patterns in the canine arterial tree with particular reference to hemodynamic events. Circ Res. 1972;30(1):23-33.

Chien S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol. 2007;292(3):1209-24.

Del CL, Sanchez LA, Salaices M, Kleeck RA, Exposito E, Gonzalez GC, et al. Vascular smooth muscle cell-specific progerin expression in a mouse model of Hutchinson-Gilford progeria syndrome promotes arterial stiffness: Therapeutic effect of dietary nitrite. Aging Cell. 2019;18(3):12936.

Wang JH, Goldschmidt CP, Wille J, Yin FC. Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J Biomech. 2001;34(12):1563-72.

Naruse K, Yamada T, Sokabe M. Involvement of SA channels in orienting response of cultured endothelial cells to cyclic stretch. Am J Physiol. 1998;274(5):1532-8.

Liu WF, Nelson CM, Tan JL, Chen CS. Cadherins, RhoA, and Rac1 are differentially required for stretch-mediated proliferation in endothelial versus smooth muscle cells. Circ Res. 2007;101(5):44-52.

Kamei M, Saunders WB, Bayless KJ, Dye L, Davis GE, Weinstein BM. Endothelial tubes assemble from intracellular vacuoles in vivo. Nature. 2006;442(7101):453-6.

Dvorak AM, Feng D. The vesiculo-vacuolar organelle (VVO). A new endothelial cell permeability organelle. J Histochem Cytochem. 2001;49(4):419-32.

Malek AM, Izumo S. Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. J Cell Sci. 1996;109(4):713-26.

Helmlinger G, Geiger RV, Schreck S, Nerem RM. Effects of pulsatile flow on cultured vascular endothelial cell morphology. J Biomech Eng. 1991;113(2):123-31.

Walpola PL, Gotlieb AI, Langille BL. Monocyte adhesion and changes in endothelial cell number, morphology, and F-actin distribution elicited by low shear stress in vivo. Am J Pathol. 1993;142(5):1392-400.

Zhao S, Suciu A, Ziegler T, Moore JE, Burki E, Meister JJ, et al. Synergistic effects of fluid shear stress and cyclic circumferential stretch on vascular endothelial cell morphology and cytoskeleton. Arterioscler Thromb Vasc Biol. 1995;15(10):1781-6.

Varandas E, Pereira HS, Monteiro S, Neves E, Brito L, Ferreira RB, Viegas W, Delgado M. Bisphenol A disrupts transcription and decreases viability in aging vascular endothelial cells. Int J Mol Sci. 2014;15(9):15791-805.

Collins C, Tzima E. Hemodynamic forces in endothelial dysfunction and vascular aging. Exp Gerontol. 2011;46(2-3):185-8.

Rennier K, Ji JY. Effect of shear stress and substrate on endothelial DAPK expression, caspase activity, and apoptosis. BMC Res Notes. 2013;6:10.

Bass GT, Ryall KA, Katikapalli A, Taylor BE, Dang ST, Acton ST, Saucerman JJ. Automated image analysis identifies signaling pathways regulating distinct signatures of cardiac myocyte hypertrophy. J Mol Cell Cardiol. 2012;52(5):923-30.

Jia G, Aroor AR, Jia C, Sowers JR. Endothelial cell senescence in aging-related vascular dysfunction. Biochim Biophys Acta Mol Basis Dis. 2019;1865(7):1802-9.

Tzur YB, Wilson KL, Gruenbaum Y. SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton. Nat Rev Mol Cell Biol. 2006;7(10):782-8.

Carey SP, Kraning RCM, Williams RM, Reinhart KCA. Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture. Biomaterials. 2012;33(16):4157-65.

Jiang Y, Ji JY. Expression of Nuclear Lamin Proteins in Endothelial Cells is Sensitive to Cell Passage and Fluid Shear Stress. Cell Mol Bioeng. 2017;11(1):53-64.

Ives CL, Eskin SG, McIntire LV. Mechanical effects on endothelial cell morphology: in vitro assessment. In Vitro Cell Dev Biol. 1986;22(9):500-7.

Alessio P. Aging and the endothelium. Exp Gerontol. 2004;39(2):165-71.

Heyde C. Central limit theorem Encyclo Actuarial Sci. 2006.

Khatau SB, Hale CM, Stewart HPJ, Patel MS, Stewart CL, Searson PC, et al. A perinuclear actin cap regulates nuclear shape. Proc Natl Acad Sci U S A. 2009;106(45):19017-22.

Dahl KN, Booth GEA, Ladoux B. In the middle of it all: mutual mechanical regulation between the nucleus and the cytoskeleton. J Biomech. 2010;43(1):2-8.

Davidson PM, Lammerding J. Broken nuclei--lamins, nuclear mechanics, and disease. Trends Cell Biol. 2014;24(4):247-56.

Gregory TR. Coincidence, coevolution, or causation? DNA content, cell size, and the C-value enigma. Biol Rev Camb Philos Soc. 2001;76(1):65-101.

Ingber DE, Madri JA, Folkman J. Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion. In Vitro Cell Dev Biol. 1987;23(5):387-94.