Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 18504

Share This Special Issue

Special Issue Editor

Prof. Dr. Hidenori Koyama

E-Mail Website
Guest Editor

Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo College of Medicine, Nishinomiya City, Hyogo 663-8501, Japan
Interests: molecular aspects of metabolism; cardiovascular diseases and psycho-neurological disorders

Special Issue Information

Dear colleagues,

Vascular endothelium is now recognized as a dynamically regulated organ and plays a pivotal role in a variety of physiological and pathological processes. Not only as a barrier between the circulation and issues, endothelial cells actively regulate vascular tone, blood flow, and platelet function. Dysregulation of endothelial cells is closely associated with pathological conditions such as vascular inflammation, atherosclerosis, hypertension, cardiomyopathy, microvascular diabetic complications, and cancer. Metabolic diseases such as diabetes, obesity, and dyslipidemia have the potential to cause vascular dysfunction and endothelial inflammation, which underly pathophysiology of vascular complications including atherosclerotic cardiovascular diseases. Numerous mechanisms by which metabolic abnormalities cause endothelial dysfunction, including reduced nitric oxide production, increased reactive oxygen species, induction of inflammatory pathways, and increased production of vasoconstrictors. The aim of this special issue is to collect recent topics and aspects of molecular cross-talk between metabolic components and endothelial inflammation, in relation to metabolic disorders and cardiovascular disorders.

Subtopics may include,

molecular mechanisms of endothelial inflammation
endothelial inflammation in diabetes
endothelial inflammation in obesity
endothelial inflammation and lipid metabolism
endothelial inflammation and cognitive function in metabolic disorders
endothelial inflammation and cardiomyopathy in metabolic disorders
endothelial inflammation and microvascular complications in diabetes

Prof. Dr. Karin E. Bornfeldt
Prof. Bodo Levkau
Prof. Dr. Hidenori Koyama
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

endothelial dysfunction
diabetes
obesity
dyslipidemia
atherosclerosis
cognitive function
cardiomyopathy

Published Papers (6 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

16 pages, 6219 KiB

Open AccessArticle

Endoglin Is an Important Mediator in the Final Common Pathway of Chronic Kidney Disease to End-Stage Renal Disease

by Tessa Gerrits, Isabella J. Brouwer, Kyra L. Dijkstra, Ron Wolterbeek, Jan A. Bruijn, Marion Scharpfenecker and Hans J. Baelde

Int. J. Mol. Sci. 2023, 24(1), 646; https://doi.org/10.3390/ijms24010646 - 30 Dec 2022

Cited by 1 | Viewed by 2016

Abstract

Chronic kidney disease (CKD) is a slow-developing, progressive deterioration of renal function. The final common pathway in the pathophysiology of CKD involves glomerular sclerosis, tubular atrophy and interstitial fibrosis. Transforming growth factor-beta (TGF-β) stimulates the differentiation of fibroblasts towards myofibroblasts and the production of extracellular matrix (ECM) molecules, and thereby interstitial fibrosis. It has been shown that endoglin (ENG, CD105), primarily expressed in endothelial cells and fibroblasts, can function as a co-receptor of TGF signaling. In several human organs, endoglin tends to be upregulated when chronic damage and fibrosis is present. We hypothesize that endoglin is upregulated in renal interstitial fibrosis and plays a role in the progression of CKD. We first measured renal endoglin expression in biopsy samples obtained from patients with different types of CKD, i.e., IgA nephropathy, focal segmental glomerulosclerosis (FSGS), diabetic nephropathy (DN) and patients with chronic allograft dysfunction (CAD). We showed that endoglin is upregulated in CAD patients (p < 0.001) and patients with DN (p < 0.05), compared to control kidneys. Furthermore, the amount of interstitial endoglin expression correlated with eGFR (p < 0.001) and the amount of interstitial fibrosis (p < 0.001), independent of the diagnosis of the biopsies. Finally, we investigated in vitro the effect of endoglin overexpression in TGF-β stimulated human kidney fibroblasts. Overexpression of endoglin resulted in an enhanced ACTA2, CCN2 and SERPINE1 mRNA response (p < 0.05). It also increased the mRNA and protein upregulation of the ECM components collagen type I (COL1A1) and fibronectin (FN1) (p < 0.05). Our results suggest that endoglin is an important mediator in the final common pathway of CKD and could be used as a possible new therapeutic target to counteract the progression towards end-stage renal disease (ESRD). Full article

(This article belongs to the Special Issue Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases)

► Show Figures

Figure 1

16 pages, 2823 KiB

Open AccessArticle

The Role of Interleukin-1-Receptor-Antagonist in Bladder Cancer Cell Migration and Invasion

by Lisa Schneider, Junnan Liu, Cheng Zhang, Anca Azoitei, Sabine Meessen, Xi Zheng, Catharina Cremer, Christian Gorzelanny, Sybille Kempe-Gonzales, Cornelia Brunner, Felix Wezel, Christian Bolenz, Cagatay Gunes and Axel John

Int. J. Mol. Sci. 2021, 22(11), 5875; https://doi.org/10.3390/ijms22115875 - 30 May 2021

Cited by 9 | Viewed by 3693

Abstract

Background: The interleukin-1-receptor antagonist IL1RA (encoded by the IL1RN gene) is a potent competitive antagonist to interleukin-1 (IL1) and thereby is mainly involved in the regulation of inflammation. Previous data indicated a role of IL1RA in muscle-invasive urothelial carcinoma of the bladder (UCB) as well as an IL1-dependent decrease in tissue barrier function, potentially contributing to cancer cell invasion. Objective: Based on these observations, here we investigated the potential roles of IL1RA, IL1A, and IL1B in bladder cancer cell invasion in vitro. Methods: Cell culture, real-time impedance sensing, invasion assays (Boyden chamber, pig bladder model), qPCR, Western blot, ELISA, gene overexpression. Results: We observed a loss of IL1RA expression in invasive, high-grade bladder cancer cell lines T24, UMUC-3, and HT1197 while IL1RA expression was readily detectable in the immortalized UROtsa cells, the non-invasive bladder cancer cell line RT4, and in benign patient urothelium. Thus, we modified the invasive human bladder cancer cell line T24 to ectopically express IL1RA, and measured changes in cell migration/invasion using the xCELLigence Real-Time-Cell-Analysis (RTCA) system and the Boyden chamber assay. The real-time observation data showed a significant decrease of cell migration and invasion in T24 cells overexpressing IL1RA (T24-IL1RA), compared to cells harboring an empty vector (T24-EV). Concurrently, tumor cytokines, e.g., IL1B, attenuated the vascular endothelial barrier, which resulted in a reduction of the Cell Index (CI), an impedance-based dimensionless unit. This reduction could be reverted by the simultaneous incubation with IL1RA. Moreover, we used an ex vivo porcine organ culture system to evaluate cell invasion capacity and showed that T24-IL1RA cells showed significantly less invasive capacity compared to parental T24 cells or T24-EV. Conclusions: Taken together, our results indicate an inverse correlation between IL1RA expression and tumor cell invasive capacity and migration, suggesting that IL1RA plays a role in bladder carcinogenesis, while the exact mechanisms by which IL1RA influences tumor cells migration/invasion remain to be clarified in future studies. Furthermore, we confirmed that real-time impedance sensing and the porcine ex vivo organ culture methods are powerful tools to discover differences in cancer cell migration and invasion. Full article

(This article belongs to the Special Issue Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases)

► Show Figures

Figure 1

10 pages, 1765 KiB

Open AccessArticle

Role of SIRT1 in Isoflurane Conditioning-Induced Neurovascular Protection against Delayed Cerebral Ischemia Secondary to Subarachnoid Hemorrhage

by Meizi Liu, Keshav Jayaraman, Tusar Giri, Gregory J. Zipfel and Umeshkumar Athiraman

Int. J. Mol. Sci. 2021, 22(8), 4291; https://doi.org/10.3390/ijms22084291 - 20 Apr 2021

Cited by 13 | Viewed by 2258

Abstract

We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. The aim of our current study is to examine the role of SIRT1 in isoflurane conditioning-induced neurovascular protection against SAH-induced DCI. Mice were divided into four groups: sham, SAH, or SAH with isoflurane conditioning (with and without EX-527). Experimental SAH via endovascular perforation was performed. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. EX-527, a selective SIRT1 inhibitor, 10 mg/kg was injected intraperitoneally immediately after SAH in the EX-527 group. SIRT1 mRNA expression and activity levels were measured. Vasospasm, microvessel thrombosis, and neurological outcome were assessed. SIRT1 mRNA expression was downregulated, and no difference in SIRT1 activity was noted after isoflurane exposure. Isoflurane conditioning with and without EX-527 attenuated vasospasm, microvessel thrombosis and improved neurological outcomes. Our data validate our previous findings that isoflurane conditioning provides strong protection against both the macro and micro vascular deficits induced by SAH, but this protection is likely not mediated through the SIRT1 pathway. Full article

(This article belongs to the Special Issue Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases)

► Show Figures

Figure 1

17 pages, 3355 KiB

Open AccessArticle

Bee Bread Ameliorates Vascular Inflammation and Impaired Vasorelaxation in Obesity-Induced Vascular Damage Rat Model: The Role of eNOS/NO/cGMP-Signaling Pathway

by Zaidatul Akmal Othman, Zaida Zakaria, Joseph Bagi Suleiman, Victor Udo Nna, Aminah Che Romli, Wan Syaheedah Wan Ghazali and Mahaneem Mohamed

Int. J. Mol. Sci. 2021, 22(8), 4225; https://doi.org/10.3390/ijms22084225 - 19 Apr 2021

Cited by 11 | Viewed by 2654

Abstract

Obesity and hyperlipidemia are major risk factors for developing vascular diseases. Bee bread (BB) has been reported to exhibit some biological actions, including anti-obesity and anti-hyperlipidemic. This study aims to investigate whether bee bread can ameliorate vascular inflammation and impaired vasorelaxation activity through eNOS/NO/cGMP pathway in obese rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10/group), namely: control (normal group), obese rats (OB group), obese rats treated with bee bread (0.5 g/kg/day, OB/BB group) and obese rats treated with orlistat (10 mg/kg/day, OB/OR group). The latter three groups were given a high-fat diet (HFD) for 6 weeks to induced obesity before being administered with their respective treatments for another 6 weeks. After 12 weeks of the total experimental period, rats in the OB group demonstrated significantly higher Lee obesity index, lipid profile (total cholesterol, triglyceride, low-density lipoprotein), aortic proinflammatory markers (tumor necrosis factor-α, nuclear factor-κβ), aortic structural damage and impairment in vasorelaxation response to acetylcholine (ACh). Bee bread significantly ameliorated the obesity-induced vascular damage manifested by improvements in the lipid profile, aortic inflammatory markers, and the impaired vasorelaxation activity by significantly enhancing nitric oxide release, promoting endothelial nitric oxide synthase (eNOS) and cyclic guanosine monophosphate (cGMP) immunoexpression. These findings suggest that the administration of bee bread ameliorates the impaired vasorelaxation response to ACh by improving eNOS/NO/cGMP-signaling pathway in obese rats, suggesting its vascular therapeutic role. Full article

(This article belongs to the Special Issue Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases)

► Show Figures

Figure 1

Review

Jump to: Research

15 pages, 2038 KiB

Open AccessReview

Role of Anesthetics and Their Adjuvants in Neurovascular Protection in Secondary Brain Injury after Aneurysmal Subarachnoid Hemorrhage

by Umeshkumar Athiraman and Gregory J. Zipfel

Int. J. Mol. Sci. 2021, 22(12), 6550; https://doi.org/10.3390/ijms22126550 - 18 Jun 2021

Cited by 9 | Viewed by 2192

Abstract

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or endovascular repair of their aneurysm. Given the potential impact certain anesthetics have on secondary brain injury after SAH, appropriate selection of anesthetics may prove impactful on overall outcome of these patients. This narrative review focuses on the available evidence of anesthetics and their adjuvants in neurovascular protection in aneurysmal subarachnoid hemorrhage and discusses current impact on clinical care and future investigative directions. Full article

(This article belongs to the Special Issue Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases)

► Show Figures

Figure 1

17 pages, 2021 KiB

Open AccessReview

Involvement of Cytokines in the Pathogenesis of Diabetic Macular Edema

by Hidetaka Noma, Kanako Yasuda and Masahiko Shimura

Int. J. Mol. Sci. 2021, 22(7), 3427; https://doi.org/10.3390/ijms22073427 - 26 Mar 2021

Cited by 48 | Viewed by 4825

Abstract

Diabetic macular edema (DME) is a critical complication of diabetic retinopathy, a condition that arises from the breakdown of the blood–retinal barrier and the consequent increase in vascular permeability. Over the years, attempts have been made to treat DME by various approaches, including laser photocoagulation, steroid triamcinolone acetonide, and vitrectomy. However, treatment was unsatisfactory until research identified vascular endothelial growth factor (VEGF) as a factor in the pathogenesis of DME. Intraocular anti-VEGF agents show good efficacy in DME. Nevertheless, in some patients the condition recurs or becomes resistant to treatment, suggesting that other factors may be involved. Because inflammation and retinal hypoxia are seen in DME, research has examined the potential role of cytokines and other inflammatory mediators. In this review, we provide an overview of this research and describe feedback mechanisms that may represent a target for novel treatments. Full article

(This article belongs to the Special Issue Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases)

► Show Figures

Journal Menu

Journal Browser

Recent Aspects in the Pathogenesis and Molecular Mechanism of Vascular Endothelial Inflammation in Metabolic Diseases

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (6 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI