Cyclic strain modulates tubulogenesis of endothelial cells in a 3D tissue culture model.

Angiogenesis is the formation of new blood vessels from preexisting capillaries or venules. It occurs in a mechanically dynamic environment due to blood flow, but the role of hemodynamic forces in angiogenesis remains poorly understood. We have developed a unique in vitro system for the investigation of angiogenesis under cyclic strain. In this system, tubulogenesis of vascular endothelial cells in 3D collagen gels occurs under well-defined cyclic strain, which mimics blood-pressure-induced stretch. Using this system, we demonstrate that cyclic strain results in alignment of endothelial-cord-like structures perpendicular to the principal axis of stretch. Such preferential orientation was the most evident in deep and long cord-like structures. This in vitro system, along with the novel findings of strain-modulated endothelial tube morphology, enables the formation of an experimental basis for understanding the role of cyclic strain in the regulation of angiogenesis.

[1]  I. Herman,et al.  Mechanisms of normal and tumor-derived angiogenesis. , 2002, American journal of physiology. Cell physiology.

[2]  T D Brown,et al.  Techniques for mechanical stimulation of cells in vitro: a review. , 2000, Journal of biomechanics.

[3]  Peter Carmeliet,et al.  Manipulating angiogenesis in medicine , 2004, Journal of internal medicine.

[4]  Shu Chien,et al.  Shear stress-induced c-fos activation is mediated by Rho in a calcium-dependent manner. , 2003, Biochemical and biophysical research communications.

[5]  Melody A Swartz,et al.  Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. , 2004, Microvascular research.

[6]  A L Zhou,et al.  Capillary growth in overloaded, hypertrophic adult rat skeletal muscle: An ultrastructural study , 1998, The Anatomical record.

[7]  D. Ingber.  Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. , 2002, Circulation research.

[8]  A. Mikos,et al.  Angiogenesis with biomaterial-based drug- and cell-delivery systems , 2004, Journal of biomaterials science. Polymer edition.

[9]  Robert M Nerem,et al.  Role of mechanics in vascular tissue engineering. , 2003, Biorheology.

[10]  L V McIntire,et al.  Shear stress and cyclic strain modulation of gene expression in vascular endothelial cells. , 1995, Blood purification.

[11]  L. Orci,et al.  Basic fibroblast growth factor induces angiogenesis in vitro. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Xiaodong Feng,et al.  Angiogenesis in wound healing. , 2000, The journal of investigative dermatology. Symposium proceedings.

[13]  S. Egginton,et al.  Capillary growth in relation to blood flow and performance in overloaded rat skeletal muscle. , 1998, Journal of applied physiology.

[14]  O. Hudlická.  Is Physiological Angiogenesis in Skeletal Muscle Regulated by Changes in Microcirculation? , 1998, Microcirculation.

[15]  Rod J. Rohrich,et al.  Increased Survival and Vascularity of Random‐Pattern Skin Flaps Elevated in Controlled, Expanded Skin , 1983, Plastic and reconstructive surgery.

[16]  M. Swartz,et al.  Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model. , 2003, American journal of physiology. Heart and circulatory physiology.

[17]  Roy M. Smeal,et al.  Comparison of human fibroblast ECM-related gene expression on elastic three-dimensional substrates relative to two-dimensional films of the same material. , 2003, Biomaterials.

[18]  L. Orci,et al.  Leukemia inhibitory factor (LIF) inhibits angiogenesis in vitro. , 1995, Journal of cell science.

[19]  P. Cahill,et al.  Pulsatile Flow–Induced Angiogenesis: Role of Gi Subunits , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[20]  L. Orci,et al.  Synergistic effect of hyaluronan oligosaccharides and vascular endothelial growth factor on angiogenesis in vitro. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[21]  O. Hudlická.  THE BENJAMIN W. ZWEIFACH AWARD LECTURE 1997 , 1998 .

[22]  C. T. Wagner,et al.  Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. , 1997, The Journal of clinical investigation.

[23]  L. Orci,et al.  Tumor-promoting phorbol esters induce angiogenesis in vitro , 1985, Cell.

[24]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[25]  P. Carmeliet,et al.  Molecular mechanisms of blood vessel growth. , 2001, Cardiovascular research.

[26]  D. Vittet,et al.  In Vitro Models of Vasculogenesis and Angiogenesis , 2001, Laboratory Investigation.

[27]  K J Gooch,et al.  Biomaterial-microvasculature interactions. , 2000, Biomaterials.

[28]  S Q Liu,et al.  Biomechanical basis of vascular tissue engineering. , 2000, Critical reviews in biomedical engineering.

[29]  S. Egginton,et al.  Association between Shear Stress, Angiogenesis, and VEGF in Skeletal Muscles In Vivo , 2001, Microcirculation.

[30]  Rakesh K. Jain,et al.  Quantitative angiogenesis assays: Progress and problems , 1997, Nature Medicine.

[31]  L. McIntire,et al.  Mechanical effects on endothelial cell morphology: In vitro assessment , 1986, In Vitro Cellular & Developmental Biology.

[32]  L V McIntire,et al.  Cyclical strain effects on production of vasoactive materials in cultured endothelial cells , 1992, Journal of cellular physiology.

[33]  L. McIntire,et al.  Therapeutic neovascularization: contributions from bioengineering. , 2005, Tissue engineering.

[34]  J. Folkman,et al.  Fundamental concepts of the angiogenic process. , 2003, Current molecular medicine.

[35]  S. Egginton,et al.  Unorthodox angiogenesis in skeletal muscle. , 2001, Cardiovascular research.

[36]  B. Helmke,et al.  The convergence of haemodynamics, genomics, and endothelial structure in studies of the focal origin of atherosclerosis. , 2002, Biorheology.

[37]  M S Kolodney,et al.  Isometric contraction by fibroblasts and endothelial cells in tissue culture: a quantitative study , 1992, The Journal of cell biology.

[38]  B. Sumpio,et al.  Morphological response of human endothelial cells subjected to cyclic strain in vitro. , 1991, Microvascular research.

[39]  J. Folkman.  Endogenous angiogenesis inhibitors , 2004, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[40]  Thomas J. Burkholder,et al.  Uniaxial strain system to investigate strain rate regulation in vitro , 2001 .

[41]  B. Sumpio,et al.  Effects of cyclic strain on vascular cells. , 2004, Endothelium : journal of endothelial cell research.

[42]  Y. Ng,et al.  Therapeutic angiogenesis for cardiovascular disease , 2001, Current controlled trials in cardiovascular medicine.

[43]  T. Skalak,et al.  The Role of Mechanical Stresses in Microvascular Remodeling , 1996, Microcirculation.

[44]  Joe Tien,et al.  Mechanotransduction at cell-matrix and cell-cell contacts. , 2004, Annual review of biomedical engineering.

[45]  H. Schlichting.  Boundary Layer Theory , 1955 .

[46]  Andrew Yee,et al.  cDNA microarray analysis of endothelial cells subjected to cyclic mechanical strain: importance of motion control. , 2005, Physiological genomics.

[47]  K. Burridge,et al.  Rho-mediated Contractility Exposes a Cryptic Site in Fibronectin and Induces Fibronectin Matrix Assembly , 1998, The Journal of cell biology.

[48]  S. Egginton,et al.  Differential involvement of MMP-2 and VEGF during muscle stretch- versus shear stress-induced angiogenesis. , 2002, American journal of physiology. Heart and circulatory physiology.

[49]  K. Tanishita,et al.  Effect of shear stress on microvessel network formation of endothelial cells with in vitro three-dimensional model. , 2004, American journal of physiology. Heart and circulatory physiology.

[50]  J. Tomasek,et al.  Mechanical properties of the extracellular matrix influence fibronectin fibril assembly in vitro. , 1995, Experimental cell research.

[51]  A. J. Reid,et al.  Endothelial cell alignment on cyclically-stretched silicone surfaces , 2004, Journal of materials science. Materials in medicine.