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?1 integrin is a sensor of blood flow direction.

ABSTRACT: Endothelial cell (EC) sensing of fluid shear stress direction is a critical determinant of vascular health and disease. Unidirectional flow induces EC alignment and vascular homeostasis, whereas bidirectional flow has pathophysiological effects. ECs express several mechanoreceptors that respond to flow, but the mechanism for sensing shear stress direction is poorly understood. We determined, by using in vitro flow systems and magnetic tweezers, that ?1 integrin is a key sensor of force direction because it is activated by unidirectional, but not bidirectional, shearing forces. ?1 integrin activation by unidirectional force was amplified in ECs that were pre-sheared in the same direction, indicating that alignment and ?1 integrin activity has a feedforward interaction, which is a hallmark of system stability. En face staining and EC-specific genetic deletion studies in the murine aorta revealed that ?1 integrin is activated and is essential for EC alignment at sites of unidirectional flow but is not activated at sites of bidirectional flow. In summary, ?1 integrin sensing of unidirectional force is a key mechanism for decoding blood flow mechanics to promote vascular homeostasis.This article has an associated First Person interview with the first author of the paper.

SUBMITTER: Xanthis I

PROVIDER: S-EPMC6589088 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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β1 integrin is a sensor of blood flow direction.

Xanthis Ioannis I Souilhol Celine C Serbanovic-Canic Jovana J Roddie Hannah H Kalli Antreas C AC Fragiadaki Maria M Wong Raymond R Shah Dhruv R DR Askari Janet A JA Canham Lindsay L Akhtar Nasreen N Feng Shuang S Ridger Victoria V Waltho Jonathan J Pinteaux Emmanuel E Humphries Martin J MJ Bryan Matthew T MT Evans Paul C PC

Journal of cell science 20190603 11

Endothelial cell (EC) sensing of fluid shear stress direction is a critical determinant of vascular health and disease. Unidirectional flow induces EC alignment and vascular homeostasis, whereas bidirectional flow has pathophysiological effects. ECs express several mechanoreceptors that respond to flow, but the mechanism for sensing shear stress direction is poorly understood. We determined, by using <i>in vitro</i> flow systems and magnetic tweezers, that β1 integrin is a key sensor of force di ...[more]

PMID: 31076511

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?1 integrin is a sensor of blood flow direction.

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β1 integrin is a sensor of blood flow direction.

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