Directing Vascular Cells by Cyclic Tensile Strain:Contextual Role in Angiogenesis.

DIRECTING VASCULAR CELLS BY CYCLIC TENSILE STRAIN: CONTEXTUAL ROLE IN ANGIOGENESIS;Biomedical Engineering;Chemical Engineering;Engineering;Chemical Engineering

Yung, Yu ChingLahann, Joerg ;

University of Michigan

关键词: DIRECTING VASCULAR CELLS BY CYCLIC TENSILE STRAIN: CONTEXTUAL ROLE IN ANGIOGENESIS;    Biomedical Engineering;    Chemical Engineering;    Engineering;    Chemical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/58542/yyung_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Mechanical stretch, a normal physiologic signal in the vascular system, regulates vascular development and regeneration, but the mechanisms underlying these endothelial (EC) and smooth muscle cell (SMC) responses remain unclear.We hypothesized that cyclic tensile strain can regulate autocrine or paracrine signaling between vascular cells to activate concerted angiogenic responses.In order to systematically examine vascular cell response to cyclic tensile strain, a high precision computer controlled strain device was designed and elastomeric substrates to present defined strain profiles, for 2D and 3D studies, were created.It has been demonstrated that cyclic strain can alter EC phenotype and Angiopoietin-2 (Ang-2) expression, and the alterations in Ang-2 mediated changes in EC migration, and in vitro capillary formation.Knockdown of endogenous Ang-2 expression via RNAi, however, decreased EC responsiveness to strain mediated EC angiogenic processes.We concluded that autocrine signaling via activation of Ang-2 may be one of the mechanistic pathways by which ECs transduce mechanical strain signals to process early angiogenic responses.Cyclic strain also regulated EC secretion of platelet derived growth factor (PDGF), a known chemotactant for SMCs. Application of strain gradients on isolated vascular EC and SMC colonies in co-culture regulated EC secretion of chemotactic gradients, and this gradient directed SMC recruitment towards strain-mediated EC migration.It is concluded that cyclic strain can modulate the intercellular communication between ECs and SMCs by mediating chemotactic paracrine factors.Taken together, our studies show that the application of precise local cyclic tensile strain signals enables one to regulate the behavior of cells at the molecular level by regulating autocrine signals (EC to EC) via Ang-2 and paracrine signals (EC to SMC) via PDGF to give vascular cells directional cues to direct angiogenic phenotypes at physiologic length scales.