Rosuvastatin Improves Endothelial Dysfunction in Diabetes by Normalizing
Endoplasmic Reticulum Stress via Calpain-1 Inhibition

Zhao, Zhao; Wang, Xinpeng; Lu, Meili; Gao, Yuxia

doi:10.2174/0113816128250494231016065438

Cited by 3 publications

(1 citation statement)

References 38 publications

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“…On the other hand, the incidence of side effects seems lower with rosuvastatin than with atorvastatin [32], a finding also reached in real-life studies [33]. Likewise, rosuvastatin has not only demonstrated direct positive effects on the lipid profile, but could have additional benefits, due to its anti-inflammatory, antioxidant, antithrombotic and vascular protective properties, among other aspects [34][35][36][37][38].…”

Section: Efficacymentioning

confidence: 91%

Rosuvastatin-Based Lipid-Lowering Therapy for the Control of LDL Cholesterol in Patients at High Vascular Risk

Mostaza,

Escobar

2024

JCM

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Vascular diseases are the leading cause of death in Spain. Hypercholesterolemia is not only a cardiovascular risk factor, but also underlies the etiopathogenesis of atherosclerosis. Therefore, reducing LDL cholesterol (LDL-C) to the goals recommended by clinical practice guidelines, is essential to decrease the risk of vascular complications. Despite this, current LDL-C control is scarce, even in subjects with high and very high risk. This is mainly due to an insufficient intensification of lipid-lowering treatment. In this context, it is essential to prescribe the appropriate therapy, adjusted to patient’s needs based on their LDL-C and their vascular risk. Rosuvastatin, alone or in combination with ezetimibe, provides intensive LDL-C reductions (up to 50–55% and 60–75%, respectively), with a low risk of side effects and in an efficient manner, in patients both without and with established atherosclerotic vascular disease.

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Section: Efficacymentioning

confidence: 91%

Rosuvastatin-Based Lipid-Lowering Therapy for the Control of LDL Cholesterol in Patients at High Vascular Risk

Mostaza,

Escobar

2024

JCM

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Retinoic Acid Improves Vascular Endothelial Dysfunction by Inhibiting PI3K/AKT/YAP-mediated Ferroptosis in Diabetes Mellitus

Zhang,

Liu,

Liu

et al. 2025

CPD

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Background: Vascular endothelial dysfunction is the initial factor involved in cardiovascular injury in patients with diabetes. Retinoic acid is involved in improving vascular complications in patients with diabetes, but its protective mechanism is still unclear. This study aimed to evaluate the effect and mechanism of All-Trans Retinoic Acid (ATRA) on endothelial dysfunction induced by diabetes. Methods: In the present study, streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were observed, and the effects of ATRA on HG-induced endothelial dysfunction and ferroptosis were evaluated. Results: ATRA treatment improved impaired vasorelaxation in diabetic aortas in an endothelium-dependent manner, and this effect was accompanied by an increase in the NO concentration and eNOS expression. Ferroptosis, characterized by lipid peroxidation and iron overload induced by HG, was improved by ATRA administration, and a ferroptosis inhibitor (ferrostatin-1, Fer-1) improved endothelial function to a similar extent as ATRA. In addition, the inactivation of phosphoinositol-3-kinase (PI3K)/protein kinases B (AKT) and Yes-Associated Protein (YAP) nuclear localization induced by HG were reversed by ATRA administration. Vascular ring relaxation experiments showed that PI3K/AKT activation and YAP inhibition had similar effects on ferroptosis and endothelial function. However, the vasodilative effect of retinoic acid was affected by PI3K/AKT inhibition, and the inhibitory effects of ATRA on ferroptosis and the improvement of endothelial function were dependent on the retinoic acid receptor. Conclusion: ATRA could improve vascular endothelial dysfunction by inhibiting PI3K/AKT/YAP-mediated ferroptosis induced by HG, which provides a new idea for the treatment of vascular lesions in diabetes.

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Bioinformatical analysis and experimental validation of endoplasmic reticulum stress-related biomarker genes in type 2 diabetes mellitus

Yao,

Xu,

Zhang

et al. 2024

Front. Genet.

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IntroductionEndoplasmic reticulum stress (ERS) is a prominent etiological factor in the pathogenesis of diabetes. Nevertheless, the mechanisms through which ERS contributes to the development of diabetes remain elusive.MethodsTranscriptional expression profiles from the Gene Expression Omnibus (GEO) datasets were analyzed and compared to obtain the differentially expressed genes (DEGs) in T2DM. Following the intersection with ERS associated genes, the ERS related T2DM DEGs were identified. Receiver operating characteristic (ROC) and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were performed to screen out the ERS related biomarker genes and validate their diagnostic values. Gene expression level was detected by qPCR and Elisa assays in diabetic mice and patient serum samples.ResultsBy analyzing the transcriptional expression profiles of the GEO datasets, 49 T2DM-related DEGs were screened out in diabetic islets. RTN1, CLGN, PCSK1, IAPP, ILF2, IMPA1, CCDC47, and PTGES3 were identified as ERS-related DEGs in T2DM, which were revealed to be involved in protein folding, membrane composition, and metabolism regulation. ROC and LASSO analysis further screened out CLGN, ILF2, and IMPA1 as biomarker genes with high value and reliability for diagnostic purposes. These three genes were then demonstrated to be targeted by the transcription factors and miRNAs, including CEBPA, CEBPB, miR-197-5p, miR-6133, and others. Among these miRNAs, the expression of miR-197-5p, miR-320c, miR-1296-3P and miR-6133 was down-regulated, while that of miR-4462, miR-4476-5P and miR-7851-3P was up-regulated in diabetic samples. Small molecular drugs, including D002994, D001564, and others, were predicted to target these genes potentially. qPCR and Elisa analysis both validated the same expression alteration trend of the ERS-related biomarker genes in diabetic mice and T2DM patients.DiscussionThese findings will offer innovative perspectives for clinical diagnosis and treatment strategies for T2DM.

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Rosuvastatin Improves Endothelial Dysfunction in Diabetes by Normalizing Endoplasmic Reticulum Stress via Calpain-1 Inhibition

Cited by 3 publications

References 38 publications

Rosuvastatin-Based Lipid-Lowering Therapy for the Control of LDL Cholesterol in Patients at High Vascular Risk

Rosuvastatin-Based Lipid-Lowering Therapy for the Control of LDL Cholesterol in Patients at High Vascular Risk

Retinoic Acid Improves Vascular Endothelial Dysfunction by Inhibiting PI3K/AKT/YAP-mediated Ferroptosis in Diabetes Mellitus

Bioinformatical analysis and experimental validation of endoplasmic reticulum stress-related biomarker genes in type 2 diabetes mellitus

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