The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS–Ser-633 phosphorylation and nitric oxide production

Kong, Xiangquan; Chen, Liang; Ye, Peng; Wang, Zhimei; Zhang, Junjie; Ye, Fei; Chen, Shao‐Liang

doi:10.1091/mbc.e16-04-0241

Cited by 28 publications

(29 citation statements)

References 38 publications

(53 reference statements)

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“…These sites are characterized by LSS, which is correlated with reduced glycocalyx dimensions, potentially contributing to leukocyte adhesion and atherosclerotic-lesion development (17). Our previous studies found that LSS activation of HYAL2 degraded HA within the endothelial glycocalyx layer, decreasing eNOS-Ser633 phosphorylation and NO production (7). In the present study, we provided further evidence that glycocalyx impairment in response to LSS is mediated through the inactivation of AMPK and an increase in NHE1mediated HA degradation.…”

Section: Discussionsupporting

confidence: 70%

“…Our previous study had suggested that HYAL2 participates in glycocalyx impairment in response to LSS (7). In the present study, we incubated HUVECs with 50 mM of the HYAL2 inhibitor hyaluromycin for 3 h prior to a 30-min LSS exposure.…”

Section: Lss Activates Hyal2 To Degrade Endothelial Glycocalyxmentioning

confidence: 82%

“…However, it is also generally accepted that low shear stress (LSS; ,5 dyn/cm 2 ) plays a key role in early atherosclerosis by reducing the dimension of the endothelial glycocalyx (5), primarily through degradation of HA in the glycocalyx (6). Our previous studies have found that LSS degraded HA within the endothelial glycocalyx via the hyaluronidase 2 (HYAL2) pathway and further proved that LSS-induced glycocalyx impairment resulted in dephosphorylation of eNOS-Ser633 and decreased NO production (7). However, how HYAL2 is activated by LSS remains unclear.…”

mentioning

confidence: 85%

“…The parallel-plate flow chamber designed by Naturethink (Shanghai, China) was previously described by Kong et al (7), and a sketch is shown in Supplemental Fig. S1.…”

Section: Cell Culture and Lss Studiesmentioning

confidence: 99%

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AMP‐activated protein kinase regulates glycocalyx impairment and macrophage recruitment in response to low shear stress

et al. 2019

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Low shear stress (LSS) increases degradation of the endothelial glycocalyx, leading to production of endothelial inflammation and atherosclerosis. However, the underlying mechanisms of how LSS diminishes the endothelial glycocalyx remain unclear. We showed that LSS inactivated AMPK, enhanced Na+‐H+ exchanger (NHE)1 activity, and induced glycocalyx degradation. Activation of AMPK prevented LSS‐induced NHE1 activity and endothelial glycocalyx impairment. We further identified hyaluronidase 2 (HYAL2) as a mediator of endothelial glycocalyx impairment in HUVECs exposed to LSS. Inactivation of AMPK by LSS up‐regulates the activity of HYAL2, which acts downstream of NHE1. We characterized a left common carotid artery partial ligation (PL) model of LSS in C57BL/6 mice. The results showed decreased expression of hyaluronan (HA) in the endothelial glycocalyx and decreased thickness of the endothelial glycocalyx in PL mice. Pharmacological activation of AMPK by ampkinone not only attenuated glycocalyx impairment due to HA degradation but also blocked vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression increase and macrophage recruitment in the endothelia of PL mice. Our results revealed that AMPK dephosphorylation induced by LSS activates NHE1 and HYAL2 to promote HA degradation and glycocalyx injury, which may contribute to endothelial inflammatory reaction and macrophage recruitment.—Zhang, J., Kong, X., Wang, Z., Gao, X., Ge, Z., Gu, Y., Ye, P., Chao, Y., Zhu, L., Li, X., Chen, S. AMP‐activated protein kinase regulates glycocalyx impairment and macrophage recruitment in response to low shear stress. FASEB J. 33, 7202–7212 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 70%

Section: Lss Activates Hyal2 To Degrade Endothelial Glycocalyxmentioning

confidence: 82%

mentioning

confidence: 85%

“…The parallel-plate flow chamber designed by Naturethink (Shanghai, China) was previously described by Kong et al (7), and a sketch is shown in Supplemental Fig. S1.…”

Section: Cell Culture and Lss Studiesmentioning

confidence: 99%

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AMP‐activated protein kinase regulates glycocalyx impairment and macrophage recruitment in response to low shear stress

et al. 2019

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“…We further discovered that LSS strongly activated hyaluronidase 2 to degrade HA in the glycocalyx. The dephosphorylation of eNOS‐Ser‐633 under LSS was triggered after HA degradation by hyaluronidase, and prevented by repairing the glycocalyx with high molecular weight hyaluronan …”

Section: Discussionmentioning

confidence: 99%

Relationship between the endothelial glycocalyx and the extent of coronary atherosclerosis

et al. 2018

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Endothelial Glycocalyx

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Ramirez‐Perez³

et al. 2022

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The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS–Ser-633 phosphorylation and nitric oxide production

Abstract: This study examines the mechanism of glycocalyx injury under low shear stress (LSS). LSS-induced changes of eNOS phosphorylation and NO production are based on the deficiency of the glycocalyx barrier.

Cited by 28 publications

References 38 publications

AMP‐activated protein kinase regulates glycocalyx impairment and macrophage recruitment in response to low shear stress

AMP‐activated protein kinase regulates glycocalyx impairment and macrophage recruitment in response to low shear stress

Relationship between the endothelial glycocalyx and the extent of coronary atherosclerosis

Endothelial Glycocalyx

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