Upregulation of SCUBE2 expression in dyslipidemic type 2 diabetes mellitus is associated with endothelin-1

Ali, Hirowati; Rustam, Raflis; Aprilia, Dinda; Arizal, Chairani; Gusadri, Irma Bakti; Utami, Putra Rahmadea

doi:10.1016/j.dsx.2019.07.058

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…Once again either FL-Shh or N-Shh may have acted as 43 kDa FL-Dhh competitive antagonists. Moreover, while Hh signalling is mostly shown to be good for the cardiovascular system, Scube2 which was shown to be upregulated in the setting of type 2 diabetes 46 and atherosclerosis 47 , has been associated with endothelial dysfunction 46 and has a strong proangiogenic activity 48,49 . Since Scube2 promotes soluble 19 kDa cholesterol-esterified N-Shh release, these results are actually fully consistent with the conclusion of the present study i.e.…”

Section: Discussionmentioning

confidence: 99%

Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability

Hollier

Chapouly

Diop

et al. 2020

Cardiovascular Research

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The therapeutic potential of Hedgehog (Hh) signalling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signalling in vascular biology remain poorly understood. Aims The purpose of the present paper is to clarify some conflicting literature data. Methods and Results : With this goal we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hedgehog (N-Shh) and endogenous endothelial-derived Desert Hedgehog (Dhh) induce opposite effects in endothelial cells (ECs). Notably, endothelial Dhh acts under its full-length soluble form (FL-Dhh) and activates Smoothened in ECs, while N-Shh inhibits it. At molecular level, N-Shh prevents FL-Dhh binding to Patched-1 demonstrating that N-Shh acts as competitive antagonist to FL-Dhh. Besides, we found that even though FL-Hh ligands and N-Hh ligands all bind Patched-1, they induce distinct Patched-1 localization. Finally, we confirmed that in a pathophysiological setting i.e. brain inflammation, astrocyte-derived N-Shh act as a FL-Dhh antagonist. Conclusion The present study highlights for the first time that FL-Dhh and N-Hh ligands have antagonistic properties especially in ECs. Translational Perspective As a consequence, Hh ligands or forms of Hh ligands cannot be used instead of another for therapeutic purposes.

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Section: Discussionmentioning

confidence: 99%

Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability

Hollier

Chapouly

Diop

et al. 2020

Cardiovascular Research

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show abstract

“…Moreover, while Hh signaling is mostly shown to be good for the cardiovascular system, Scube2 was shown to be upregulated in the setting of type 2 diabetes 34 and atherosclerosis 35 . Besides Scube2 has been associated with endothelial dysfunction 34 and has a strong proangiogenic activity 36,37 .…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell response to Hedgehog ligands depends on their processing

Hollier

Chapouly

Diop

et al. 2020

Preprint

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Rationale:The therapeutic potential of Hedgehog (Hh) signaling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signaling in vascular biology remain poorly understood. Objective: The purpose of the present paper is to clarify some conflicting literature data. Findings: With this goal we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hedgehog (N-Shh) and endogenous endothelial-derived Desert Hedgehog (Dhh) induce opposite effects in endothelial cells. (ECs). Notably, endothelial Dhh acts under its full-length soluble form (FL-Dhh) and activates Smoothened in ECs, while N-Shh inhibits it. At molecular level, N-Shh prevents FL-Dhh binding to Patched-1 demonstrating that N-Shh acts as competitive antagonist to FL-Dhh. Besides, we found that even though FL-Hh ligands and N-Hh ligands all bind Patched-1, they induce specific Patched-1 localization. Finally, we confirmed that in a pathophysiological setting i.e. brain inflammation, astrocyte-derived N-Shh act as a FL-Dhh antagonist. Conclusion: The present study highlights for the first time that FL-Dhh and N-Hh ligands have antagonistic properties especially in ECs, and demonstrates that Hh ligands or forms of Hh ligands cannot be used instead of another for therapeutic purposes.

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“…VLDL and LDL were mathematically calculated [LDL-C (mg/dl)] = TC mg/dl -[HDL-C mg/dl] + TG/5 (mg/dl). MDA was measured [18], by a MDA reaction with thiobarbituric acid in an acidic condition to produce a pink color chromophore, which spectrophotometrically detected at 535 nm.…”

Section: Lipid Profile Measurementmentioning

confidence: 99%

Increasing Vascular Complications Depends on The Duration Disease of Having Been Diabetic Type 2

Ismail

Jawad

Hammood³

2020

MJS

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Angiopathy is a major complication in (T2-DM), Endothelin-1 (ET-1) is considered the main vasoconstrictor (a mitogenic endothelium-derived peptide is mostly, produced by endothelial cells, as well by vascular smooth muscle cells, macrophages, and other cells). Previous studies suggested a link between T2-DM and ET-1. This paper aims to study the association between Endothelin-1 (ET-1) as a marker of endothelial dysfunction and the duration disease among patients with T2-DM, and to identify the effects of obesity and insulin resistance on elevated Endothelin level. The study includes 96 patients with T2-DM, aged between (45-70) years, (56.73 ± 9.14 years) is an average duration of having T2-DM (14.541± 11.462) years, and 96 healthy control subjects, aged (45-70) years, (56.42 ± 8.74 years). We show that the excess of ET-1 level was clearly linked with the duration of T2-DM, where the plasma Endothelin level was significantly changed among the studied groups (according to their duration) (11.607 ±0.783), (13.641± 0.729), (17.736 ± 3.409), (33.816 ± 12.902), (81.165 ± 35.404), and (156.783 ± 12.671) pg/mL respectively. Plasma ET-1 levels significant is positively correlated with T2-DM (R² = 0.9711, p ≤ 0.01), with obesity, insulin resistance, age, HOMO-IR, hypertension, and HDL level (p ≤ 0.05). As a conclusion, the plasma ET-1 level was significantly elevated as long as having been T2-DM.

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Upregulation of SCUBE2 expression in dyslipidemic type 2 diabetes mellitus is associated with endothelin-1

Cited by 8 publications

References 10 publications

Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability

Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability

Endothelial cell response to Hedgehog ligands depends on their processing

Increasing Vascular Complications Depends on The Duration Disease of Having Been Diabetic Type 2

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