Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin‐1, and endothelial dysfunction in streptozotocin treated rats

Shamsaldeen, Yousif A.; Ugur, Rosemary; Benham, Christopher D.; Lione, Lisa

doi:10.1002/dmrr.2995

Cited by 16 publications

(15 citation statements)

References 30 publications

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“…Therefore, maintaining blood glucose within a normal range is the foremost objective in the treatment of T2D ( Kahn et al, 2014 ). STZ-induced diabetic rats were associated with high levels of FBG, TC, TG, and LDL-C, which are consistent with other animal studies ( Erfani Majd et al, 2018 ; Shamsaldeen et al, 2018 ).…”

Section: Discussionsupporting

confidence: 92%

Gastrodin Ameliorates Cognitive Dysfunction in Diabetes Rat Model via the Suppression of Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation

Ye¹,

Meng

Zhai

et al. 2018

Front. Pharmacol.

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Patients with diabetes mellitus (DM) are at high risk for cognitive dysfunction. Endoplasmic reticulum stress (ERS) and inflammation play crucial roles in DM. Gastrodin (Gas), the main component of Gastrodia elata, possesses anti-oxidative stress, anti-inflammatory, and neuroprotective effects. This present study aims to investigate whether Gas could ameliorate cognitive dysfunction in DM and to explore its underlying mechanisms. Rats with streptozotocin-induced type 2 DM were used in this study. After administration of Gas for 5 weeks, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in serum, TNF-α, IL-1β, MDA and SOD in the hippocampus were measured. Morris water maze, hematoxylin and eosin (HE) and Nissl staining were performed to assess the effects of Gas on cognitive function and hippocampal neuronal apoptosis. Protein levels of GLUT3, brain derived neurotrophic factor (BDNF), GRP78, PERK, P-PERK, TXNIP, ASC, NLRP3, CHOP, Bcl-2 and Bax were measured by using Western blot. The results showed that Gas could improve hyperglycemia and dyslipidemia in DM rats, as the levels of TC, TG LDL-C in serum were decreased. TNF-α, IL-1β, MDA contents in the hippocampus were decreased, and SOD contents was increased in the hippocampus of DM rats. Inflammation, oxidative stress, ERS, and apoptosis were observed in the hippocampus of DM rats, accompanied with decreased expression of BDNF and GLUT3. Gas improved the cognitive deficits caused by diabetes and inhibited inflammation, oxidative stress, ERS, and apoptosis in the hippocampus. Furthermore, Gas substantially increased the expression of GLUT3, and inhibited hippocampal ERS and ERS-mediated apoptosis. Additionally, Gas increased the expression of BDNF and decreased the activation of NLRP3 inflammasome. These results suggested that by inhibiting ERS and NLRP3 inflammasome activation and increasing the expression of BDNF and GLUT3, Gas exhibits neuroprotective effects against cognitive dysfunction in DM.

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Section: Discussionsupporting

confidence: 92%

Gastrodin Ameliorates Cognitive Dysfunction in Diabetes Rat Model via the Suppression of Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation

Ye¹,

Meng

Zhai

et al. 2018

Front. Pharmacol.

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“…The vascular complications of type 2 diabetes can lead to microvascular and macrovascular damage and are major causes of disability and death in type 2 diabetes patients (2,3). Endothelial dysfunction renders diabetics vulnerable to limb infections and end-organ damage, such as nephropathy, neuropathy and retinopathy (4). In addition, diabetic macrovascular disease resembles atherosclerotic lesions both morphologically and functionally (5), and oxidized low-density lipoprotein (ox-LDL) is a key component involved in the genesis of atherosclerotic lesions and is cytotoxic to various cell types, such as endothelial cells (ECs), and is therefore suggested to contribute to endothelial dysfunction (6).…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV inhibits oxidized low‑density lipoprotein‑induced endothelial damage via upregulation of miR‑140‑3p

Qian

Cai

et al. 2019

Int J Mol Med

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Oxidized low-density lipoprotein (ox-LdL)-mediated endothelial cell injury has an important role in the vascular complications of type 2 diabetes. Astragaloside IV (ASV) is an active component of Radix Astragali, which has been demonstrated to exert protective effects against endothelial damage. The present study explored whether microRNAs (miRNAs) are involved in mediating the protective effects of ASV on ox-LdL-induced damage in human umbilical vein endothelial cells (HUVEcs). RNA sequencing and reverse transcription-quantitative PcR analyses revealed that ox-LdL treatment significantly downregulated miR-140-3p expression in HUVECs. miR-140-3p overexpression promoted cell proliferation and inhibited apoptosis in ox-LdL-induced HUVEcs. However, inhibition of miR-140-3p expression could reverse the effects of ASV on ox-LdL-induced HUVEcs and reactivate ASV-inhibited PI3K/Akt signaling in ox-LdL-induced HUVECs. In addition, Krüppel-like factor 4 (KLF4) was identified as a target of miR-140-3p in ox-LDL-treated HUVECs. Subsequent experiments revealed that KLF4 overexpression partially counteracted the protective effects of miR-140-3p or ASV treatment in ox-LdL-induced HUVEcs. Taken together, the current findings demonstrated that the protective effects of ASV on HUVECs were dependent on miR-140-3p upregulation and subsequent inhibition of KLF4 expression, which in turn suppressed the PI3K/Akt signaling pathway. The present results shed light to the molecular mechanism by which ASV alleviated ox-LdL-induced endothelial cell damage.

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“…Caveolin-1 is the main functional protein of caveolae, and a loss of caveolin-1 results in the loss of caveolae. Direct binding of eNOS to caveolin-1 is a well-accepted mechanism for inactivating eNOS, while the absence of caveolin-1 is thought to promote eNOS dysfunction [27]. In this study, we assayed the eNOS membrane expression and its association with caveolin-1 to determine its activation state.…”

Section: Discussionmentioning

confidence: 99%

Oscillatory Shear Stress Induces Oxidative Stress via TLR4 Activation in Endothelial Cells

Wang

Kong

et al. 2019

Mediators of Inflammation

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Background. Oscillatory shear stress (OSS) disrupts endothelial homeostasis and promotes oxidative stress, which can lead to atherosclerosis. In atherosclerotic lesions, Toll-like receptor 4 (TLR4) is highly expressed. However, the molecular mechanism by which TLR4 modulates oxidative changes and the cell signaling transudation upon OSS is yet to be determined. Methods and Results. Carotid artery constriction (CAC) surgery and a parallel-plate flow chamber were used to modulate shear stress. The results showed that OSS significantly increased the oxidative burden, and this was partly due to TLR4 activation. OSS activated NOX2 and had no significant influence to NOX1 or NOX4 in endothelial cells (ECs). OSS phosphorylated caveolin-1, promoted its binding with endothelial nitric oxide synthase (eNOS), and resulted in deactivation of eNOS. TLR4 inhibition restored levels of nitric oxide (NO) and superoxide dismutase (SOD) in OSS-exposed cells. Conclusion. TLR4 modulates OSS-induced oxidative stress by activating NOX2 and suppressing eNOS.

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Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin‐1, and endothelial dysfunction in streptozotocin treated rats

Abstract: The elevated serum Ox-LDL in hyperglycaemic STZ-diabetic rats may contribute to diabetic endothelial dysfunction, possibly through downregulation of endothelial CAV-1 and eNOS.

Cited by 16 publications

References 30 publications

Gastrodin Ameliorates Cognitive Dysfunction in Diabetes Rat Model via the Suppression of Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation

Gastrodin Ameliorates Cognitive Dysfunction in Diabetes Rat Model via the Suppression of Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation

Astragaloside IV inhibits oxidized low‑density lipoprotein‑induced endothelial damage via upregulation of miR‑140‑3p

Oscillatory Shear Stress Induces Oxidative Stress via TLR4 Activation in Endothelial Cells

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