Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production

Bartosch, Anne Marie W.; Mathews, Rick; Mahmoud, Marwa; Cancel, Limary M.; Haq, Zahin S.; Tarbell, John M.

doi:10.1038/s41598-021-90941-w

Cited by 34 publications

(19 citation statements)

References 41 publications

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“…In a previous in vitro study using the same kidney carcinoma cells, it was demonstrated that the HS proteoglycan core protein glypican 1, not syndecan 1, is the glycocalyx component that transmits the force to the cell where mechanotransduction proceeds [40] . This is consistent with a recent study of shear stress on endothelial cells that showed glypican 1 to be the mechanotransmitter mediating shear-induced nitric oxide production [41] . In [2] we showed that the cancer cell surface receptor for HA, CD44, is a transmitter of force sensed by HA to the cell.…”

Section: Discussionsupporting

confidence: 93%

Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Moran

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Huang

et al. 2022

Matrix Biology Plus

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Highlights Mechanotransduction through cell surface GAGs is a potential driver of metastasis. SAHA, a histone deacetylase inhibitor, reduces tumor cell NDST1 and HS. SAHA blocked metastasis of highly metastatic renal carcinoma cells in a mouse model. Reduction of hyaluronic acid suppresses metastasis in a mouse kidney cancer model.

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Section: Discussionsupporting

confidence: 93%

Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Moran

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Huang

et al. 2022

Matrix Biology Plus

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“…However, in large cerebral arteries of eBACE1 −/− mice, levels of eNOS phosphorylated at S1177 were also not increased. The exact reasons for apparent discrepancy between the results obtained in the systemic blood vessels (previous studies 19–23 ) and the results obtained in the cerebral blood vessels lacking BACE1 (present study) are unknown and remain to be determined.…”

Section: Discussioncontrasting

confidence: 79%

Inactivation of BACE1 increases expression of endothelial nitric oxide synthase in cerebrovascular endothelium

d’Uscio

Sun

et al. 2022

J Cereb Blood Flow Metab

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Cerebrovascular effects of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inactivation have not been systematically studied. In the present study we employed cultured human brain microvascular endothelial cells (BMECs), BACE1-knockout (BACE1−/−) mice and conditional (tamoxifen-induced) endothelium-specific BACE1-knockout (eBACE1−/−) mice to determine effect of BACE1 inhibition on expression and function of endothelial nitric oxide synthase (eNOS). Deletion of BACE1 caused upregulation of eNOS and glypican-1 (GPC1) in human BMECs treated with BACE1-siRNA, and cerebral microvessels of male BACE1−/− mice and male eBACE1−/− mice. In addition, BACE1siRNA treatment increased NO production in human BMECs. These effects appeared to be independent of amyloid β-peptide production. Furthermore, adenoviral-mediated overexpression of BACE1 in human BMECs down-regulated GPC1 and eNOS. Treatment of human BMECs with GPC1siRNA suppressed mRNA and protein levels of eNOS. In basilar arteries of male eBACE1−/− mice, endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to NO donor, DEA-NONOate, were not affected, consistent with unchanged expression of eNOS and phosphorylation of eNOS at Ser1177 in large cerebral arteries. In aggregate, our findings suggest that under physiological conditions, inactivation of endothelial BACE1 increases expression of eNOS in cerebral microvessels but not in large brain arteries. This effect appears to be mediated by increased GPC1 expression.

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“…It has been widely demonstrated that the CD31-targeting antibodies block the lymphocyte transmigration restoring the immunomodulatory effects ( 26 , 34 – 36 ). Intriguingly, in the presence of pathological wall shear stress, which is one of the eligible triggers underneath plaque rupture ( 47 , 48 ), CD31 acts as a mechanosensor on endothelial cells ( 49 – 52 ) and might mediate a platelet adhesion on the endothelial layer and thrombosis ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Monocyte-Platelet Aggregates Triggered by CD31 Molecule in Non-ST Elevation Myocardial Infarction: Clinical Implications in Plaque Rupture

Vinci

Pedicino

Bonanni

et al. 2022

Front. Cardiovasc. Med.

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Despite the recent innovations in cardiovascular care, atherothrombosis is still a major complication of acute coronary syndromes (ACS). We evaluated the involvement of the CD31 molecule in thrombotic risk through the formation of monocyte-platelet (Mo-Plt) aggregates in patients with ACS with no-ST-segment elevation myocardial infarction (NSTEMI) on top of dual anti-platelet therapy (DAPT). We enrolled 19 control (CTRL) subjects, 46 stable angina (SA), and 86 patients with NSTEMI, of which, 16 with Intact Fibrous Cap (IFC) and 19 with Ruptured Fibrous Cap (RFC) as assessed by the Optical Coherence Tomography (OCT). The expression of CD31 on monocytes and platelets was measured. Following the coronary angiography, 52 NSTEMIs were further stratified according to thrombus grade (TG) evaluation. Finally, a series of ex vivo experiments verified whether the CD31 participates in Mo-Plt aggregate formation. In patients with NSTEMI, CD31 was reduced on monocytes and was increased on platelets, especially in NSTEMI presented with RFC plaques compared to those with IFC lesions, and in patients with high TG compared to those with zero/low TG. Ex vivo experiments documented an increase in Mo-Plt aggregates among NSTEMI, which significantly decreased after the CD31 ligation, particularly in patients with RFC plaques. In NSTEMI, CD31 participates in Mo-Plt aggregate formation in spite of optimal therapy and DAPT, suggesting the existence of alternative thrombotic pathways, as predominantly displayed in patients with RFC.

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Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production

Cited by 34 publications

References 41 publications

Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Inactivation of BACE1 increases expression of endothelial nitric oxide synthase in cerebrovascular endothelium

Monocyte-Platelet Aggregates Triggered by CD31 Molecule in Non-ST Elevation Myocardial Infarction: Clinical Implications in Plaque Rupture

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