Bo Liu1, Shaoying Lu, Shuai Zheng, Zonglai Jiang, Yingxiao Wang. 1. Department of Bioengineering and Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Abstract
AIMS: High shear stress (HSS) can have significant impact on angiogenesis and atherosclerosis in collateral arteries near the bifurcation and curvature regions. Here, we investigate the spatiotemporal pattern of HSS-induced intracellular calcium alteration. METHODS AND RESULTS: Genetically encoded biosensors based on fluorescence resonance energy transfer were targeted in the cytoplasm and the endoplasmic reticulum (ER) to visualize the subcellular calcium dynamics in bovine aortic endothelial cells under HSS (65 dyn/cm(2)). Upon HSS application, the intracellular Ca(2+) concentration ([Ca(2+)](i)) increased immediately and maintained a sustained high level, while the ER-stored calcium had a significant decrease only after 300 s. The perturbation of calcium influx across the plasma membrane (PM) by the removal of extracellular calcium or the blockage of membrane channels inhibited the early phase of [Ca(2+)](i) increase upon HSS application, which was further shown to be sensitive to the magnitudes of shear stress and the integrity of cytoskeletal support. In contrast, Src, phospholipase C(PLC), and the inositol 1,4,5-trisphosphate receptor (IP(3)R) can regulate the late phase of HSS-induced [Ca(2+)](i) increase via the promotion of the ER calcium efflux. CONCLUSION: The HSS-induced [Ca(2+)](i) increase consists of two well-co-ordinated phases with different sources and mechanisms: (i) an early phase due to the calcium influx across the PM which is dependent on the mechanical impact and cytoskeletal support and (ii) a late phase originated from the ER-calcium efflux which is regulated by the Src, PLC, and IP(3)R signalling pathway. Therefore, our work presented new molecular-level insights into systematic understanding of mechanotransduction in cardiovascular systems.
AIMS: High shear stress (HSS) can have significant impact on angiogenesis and atherosclerosis in collateral arteries near the bifurcation and curvature regions. Here, we investigate the spatiotemporal pattern of HSS-induced intracellular calcium alteration. METHODS AND RESULTS: Genetically encoded biosensors based on fluorescence resonance energy transfer were targeted in the cytoplasm and the endoplasmic reticulum (ER) to visualize the subcellular calcium dynamics in bovine aortic endothelial cells under HSS (65 dyn/cm(2)). Upon HSS application, the intracellular Ca(2+) concentration ([Ca(2+)](i)) increased immediately and maintained a sustained high level, while the ER-stored calcium had a significant decrease only after 300 s. The perturbation of calcium influx across the plasma membrane (PM) by the removal of extracellular calcium or the blockage of membrane channels inhibited the early phase of [Ca(2+)](i) increase upon HSS application, which was further shown to be sensitive to the magnitudes of shear stress and the integrity of cytoskeletal support. In contrast, Src, phospholipase C(PLC), and the inositol 1,4,5-trisphosphate receptor (IP(3)R) can regulate the late phase of HSS-induced [Ca(2+)](i) increase via the promotion of the ER calcium efflux. CONCLUSION: The HSS-induced [Ca(2+)](i) increase consists of two well-co-ordinated phases with different sources and mechanisms: (i) an early phase due to the calcium influx across the PM which is dependent on the mechanical impact and cytoskeletal support and (ii) a late phase originated from the ER-calcium efflux which is regulated by the Src, PLC, and IP(3)R signalling pathway. Therefore, our work presented new molecular-level insights into systematic understanding of mechanotransduction in cardiovascular systems.
Authors: Eleni Metaxa; Hui Meng; Shashikanth R Kaluvala; Michael P Szymanski; Rocco A Paluch; John Kolega Journal: Am J Physiol Heart Circ Physiol Date: 2008-06-13 Impact factor: 4.733
Authors: Christopher G Scheitlin; Justin A Julian; Santhanam Shanmughapriya; Muniswamy Madesh; Nikolaos M Tsoukias; B Rita Alevriadou Journal: Am J Physiol Cell Physiol Date: 2016-01-06 Impact factor: 4.249
Authors: Liang Wen; Zhen Chen; Fan Zhang; Xiaopei Cui; Wei Sun; Greg G Geary; Yinsheng Wang; David A Johnson; Yi Zhu; Shu Chien; John Y-J Shyy Journal: Proc Natl Acad Sci U S A Date: 2013-06-10 Impact factor: 11.205
Authors: M Jafarnejad; W E Cromer; R R Kaunas; S L Zhang; D C Zawieja; J E Moore Journal: Am J Physiol Heart Circ Physiol Date: 2015-01-23 Impact factor: 4.733