scholarly journals Mechanics-driven mechanobiological mechanisms of arterial tortuosity

2020 ◽  
Vol 6 (49) ◽  
pp. eabd3574
Author(s):  
Dar Weiss ◽  
Cristina Cavinato ◽  
Authia Gray ◽  
Abhay B. Ramachandra ◽  
Stephane Avril ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Multimodality Imaging ◽  
Elastic Fiber ◽  
The Novel ◽  
Arterial Tortuosity ◽  
Buckling Instability ◽  
Clinical Biomarker ◽  
Underlying Mechanisms ◽  
Microstructural Integrity ◽  
Collagen Alignment

Arterial tortuosity manifests in many conditions, including hypertension, genetic mutations predisposing to thoracic aortopathy, and vascular aging. Despite evidence that tortuosity disrupts efficient blood flow and that it may be an important clinical biomarker, underlying mechanisms remain poorly understood but are widely appreciated to be largely biomechanical. Many previous studies suggested that tortuosity may arise via an elastic structural buckling instability, but the novel experimental-computational approach used here suggests that tortuosity arises from mechanosensitive, cell-mediated responses to local aberrations in the microstructural integrity of the arterial wall. In particular, computations informed by multimodality imaging show that aberrations in elastic fiber integrity, collagen alignment, and collagen turnover can lead to a progressive loss of structural stability that entrenches during the development of tortuosity. Interpreted in this way, microstructural defects or irregularities of the arterial wall initiate the condition and hypertension is a confounding factor.

scholarly journals Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

2018 ◽  
Vol 50 (6) ◽  
pp. 2390-2405 ◽  
Author(s):  
Shuping Wei ◽  
Jingjing Zhang ◽  
Biao Han ◽  
Jianxun Liu ◽  
Xiaohui Xiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Erk Signaling ◽  
The Novel ◽  
Differentiation Markers ◽  
Zinc Finger Transcription Factor ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Injury Model ◽  
Underlying Mechanisms

Background/Aims: Phenotypic switching of vascular smooth muscle cells (VSMC) plays a vital role in the development of vascular diseases. All-trans retinoic acid (ATRA) is known to regulate VSMC phenotypes. However, the underlying mechanisms remain completely unknown. Here, we have investigated the probable roles and underlying mechanisms of the novel C2H2 zinc finger transcription factor ZFP580 on ATRA-induced VSMC differentiation. Methods: VSMCs were isolated, cultured, and identified. VSMCs were infected with an adenovirus encoding ZFP580 or Ad-siRNA to silence ZFP580. The expression levels of ZFP580, SMα-actin, SM22α, SMemb, RARα, RARβ, and RARγ were assayed by Q-PCR and western blot. A rat carotid artery injury model and morphometric analysis of intimal thickening were also used in this study. Results: ATRA caused a significant reduction of VSMC proliferation and migration in a doseand time-dependent manner. Moreover, it promoted VSMC differentiation by enhancing expression of differentiation markers and reducing expression of dedifferentiation markers. This ATRA activity was accompanied by up-regulation of ZFP580, with concomitant increases in RARα expression. In contrast, silencing of the RARα gene or inhibiting RARα with its antagonist Ro41-5253 abrogated the ATRA-induced ZFP580 expression. Furthermore, ATRA binding to RARα induced ZFP580 expression via the PI3K/Akt and ERK pathways. Adenovirusmediated overexpression of ZFP580 promoted VSMC differentiation by enhancing expression of SM22α and SMα-actin and reducing expression of SMemb. In contrast, silencing ZFP580 dramatically reduced the expression of differentiation markers and increased expression of dedifferentiation markers. The classic rat carotid artery balloon injury model demonstrated that ZFP580 inhibited proliferation and intimal hyperplasia in vivo. Conclusion: The novel zinc finger transcription factor ZFP580 facilitates ATRA-induced VSMC differentiation by the RARα-mediated PI3K/Akt and ERK signaling pathways. This might represent a novel mechanism of regulation of ZFP580 by ATRA and RARα, which is critical for understanding the biological functions of retinoids during VSMC phenotypic modulation.

scholarly journals The Emerging Role of GC-MSCs in the Gastric Cancer Microenvironment: From Tumor to Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Wound Repair ◽  
Critical Role ◽  
The Novel ◽  
Potential Biomarker ◽  
Underlying Mechanisms ◽  
Gastric Cancer Progression

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.

scholarly journals COVID-19 and the Heart

2020 ◽  
pp. 1-5 ◽  
Author(s):  
Chaitanya Rojulpote ◽  
Karthik Gonuguntla ◽  
Shivaraj Patil ◽  
Abhijit Bhattaru ◽  
Paco Bravo
Keyword(s):  
Cardiovascular System ◽  
The Novel ◽  
Health Crisis ◽  
Risk Of Death ◽  
Increased Risk ◽  
The World ◽  
Significant Burden ◽  
Coronary Syndromes ◽  
Novel Virus ◽  
Underlying Mechanisms

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19) has resulted in a global health crisis. Prior to the arrival of this viral pandemic, the world was already plagued with a significant burden of cardiovascular disease. With the introduction of the novel virus, the world now faces a double jeapordy. Early reports have suggested an increased risk of death in individuals with underlying cardio-metabolic disorders. The exact effects of COVID-19 on the cardiovascular system are not well determined, however lessons from prior viral epidemics suggest that such infections can trigger acute coronary syndromes, arrhythmias and heart failure via direct and indirect mechanisms. In this article, we aimed to discuss the effects and potential underlying mechanisms of COVID -19 as well as potential implications of treatments targeted against this virus on the cardiovascular system.

Arterial wall remodelling in congenital heart disease

2018 ◽  
Author(s):  
Matina Prapa ◽  
S. Yen Ho
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Arterial Wall ◽  
Clinical Applications ◽  
Aortic Aneurysms ◽  
Common Site ◽  
Genetic Aberrations ◽  
Thoracic Aortic Aneurysms ◽  
Underlying Mechanisms

The thoracic aorta is the second most common site of aneurysm formation after the abdominal aorta. Thoracic aortic aneurysms (TAAs) often result from medial wall degeneration secondary to genetic aberrations. Over recent decades, unprecedented research in the field of connective tissue disease has led to identification of key molecular pathways involved in TAA formation. Prolonged survival of congenital heart disease patients following successful reparative surgery has also led to increased incidence of TAA in this context with extensive investigations of underlying mechanisms. This chapter summarizes breakthrough discoveries in congenital arterial wall remodelling and discusses their potential clinical applications.

scholarly journals Edible and Herbal Plants for the Prevention and Management of COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Sha Li ◽  
Chien-Shan Cheng ◽  
Cheng Zhang ◽  
Guo-Yi Tang ◽  
Hor-Yue Tan ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Dietary Supplements ◽  
Functional Foods ◽  
The Novel ◽  
Organ Protection ◽  
Global Pandemic ◽  
Potential Benefits ◽  
Herbal Plants ◽  
Dietary Components ◽  
Underlying Mechanisms

Background: The outbreak of the pandemic coronavirus disease 2019 (COVID-19) has now become a global pandemic spreading throughout the world. Unfortunately, due to the high infectiousness of the novel β-coronavirus, it is very likely to become an ordinary epidemic. The development of dietary supplements and functional foods might provide a strategy for the prevention and management of COVID-19.Scope and Approach: A great diversity of potential edible and medicinal plants and/or natural compounds showed potential benefits in managing SARS, which may also combat COVID-19. Moreover, many plants and compounds have currently been proposed to be protective against COVID-19. This information is based on data-driven approaches and computational chemical biology techniques. In this study, we review promising candidates of edible and medicinal plants for the prevention and management of COVID-19. We primarily focus on analyzing their underlying mechanisms. We aim to identify dietary supplements and functional foods that assist in managing this epidemic.Key findings and Conclusion: We infer that acetoside, glyasperin, isorhamnetin, and several flavonoid compounds may prevent and/or be effective in managing COVID-19 by targeting the viral infection, reducing the host cytokine storm, regulating the immune response, and providing organ protection. These bioactive dietary components (used either alone or in combination) might assist in the development of dietary supplements or functional foods for managing COVID-19.

scholarly journals A Novel Protocol for Detection of Senescence and Calcification Markers by Fluorescence Microscopy

2020 ◽  
Vol 21 (10) ◽  
pp. 3475
Author(s):  
Jaqueline Herrmann ◽  
Milen Babic ◽  
Markus Tölle ◽  
Kai-Uwe Eckardt ◽  
Markus van der Giet ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Arterial Wall ◽  
In Vitro Model ◽  
Evaluation Method ◽  
Cultured Cells ◽  
Current Investigation ◽  
Experimental Setting ◽  
Vitro Model ◽  
Underlying Mechanisms

Vascular calcification and stiffening of the arterial wall is a systemic phenomenon that is associated with aging and it can be increased by several risk factors. The underlying mechanisms, especially the pathways of cellular senescence, are under current investigation. Easily manageable in vitro settings help to study the signaling pathways. The experimental setting presented here is based on an in vitro model using rat vascular smooth muscle cells and the detection of senescence and osteoblastic markers via immunofluorescence and RNAscope™. Co-staining of the senescence marker p21, the osteoblastic marker osteopontin, detection of senescence-associated heterochromatin foci, and senescence-associated β-galactosidase is possible within one test approach requiring fewer cells. The protocol is a fast and reliable evaluation method for multiplexing of calcifying and senescence markers with fluorescence microscopy detection. The experimental setting enables analysis on single cell basis and allows detection of intra-individual variances of cultured cells.

scholarly journals Functionally Distinct Tendons From Elastin Haploinsufficient Mice Exhibit Mild Stiffening and Tendon-Specific Structural Alteration

2017 ◽  
Vol 139 (11) ◽  
Author(s):  
Jeremy D. Eekhoff ◽  
Fei Fang ◽  
Lindsey G. Kahan ◽  
Gabriela Espinosa ◽  
Austin J. Cocciolone ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Elastic Fiber ◽  
Mechanical Effect ◽  
Elastic Fibers ◽  
Minor Role ◽  
Tendon Mechanics ◽  
Different Types ◽  
A Minor ◽  
Collagen Alignment

Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix (IFM). While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e., vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e.g., positional, energy-storing) remains unknown. Therefore, this study purposed to evaluate the role of elastin in the mechanical properties and collagen alignment of functionally distinct supraspinatus tendons (SSTs) and Achilles tendons (ATs) from elastin haploinsufficient (HET) and wild type (WT) mice. Despite the significant decrease in elastin in HET tendons, a slight increase in linear stiffness of both tendons was the only significant mechanical effect of elastin haploinsufficiency. Additionally, there were significant changes in collagen nanostructure and subtle alteration to collagen alignment in the AT but not the SST. Hence, elastin may play only a minor role in tendon mechanical properties. Alternatively, larger changes to tendon mechanics may have been mitigated by developmental compensation of HET tendons and/or the role of elastic fibers may be less prominent in smaller mouse tendons compared to the larger bovine and human tendons evaluated in previous studies. Further research will be necessary to fully elucidate the influence of various elastic fiber components on structure–function relationships in functionally distinct tendons.

scholarly journals P001 The novel DYRK1a inhibitor VRN024219 alleviates disease severity on the IBD mouse models by modulating T-cell differentiation

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S129-S129
Author(s):  
D H Seo ◽  
H W Ma ◽  
S Kim ◽  
D H Kim ◽  
H K Kim ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Treated Group ◽  
T Cell Differentiation ◽  
Cell Transfer ◽  
The Novel ◽  
Protein Levels ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
T Cell Transfer

Abstract Background DYRK1A belongs to dual-specificity tyrosine (Y) phosphorylation regulated kinase (DYRK) family which is known to be activated through autophosphorylation of tyrosine residues in the activation loop and phosphorylates their substrates on serine and threonine residues. Other members of this family include DYRK1B, DYRK2, DYRK3, and DYRK4. Studies have revealed that DYRK kinase family plays an important role in regulating cell proliferation and apoptosis. DYRK1A has been reported to be strongly expressed in the brain and known to regulate various functions. However, the role and underlying mechanisms of DYRK1a in inflammation in general, specifically in IBD, remain poorly understood. Accordingly, we present the underlying mechanisms of DYRK1a on the course of IBD by using the novel DYRK1a inhibitor VRN024219. Methods First, we tested the effects of our compound VRN024219 on T-cell differentiation using naïve CD4 T cells extracted from the mouse spleen. Then we assessed the efficacy and mechanism of VRN024219 on the dextran sodium sulphate (DSS) and T-cell transfer-induced experimental colitis that mimics human ulcerative colitis (UC), comparing to that of Tofacitinib. Finally, we evaluated the effect of VRN024219 on pro-inflammatory cytokines such as interleukin (IL) −17A, IL-6, and tumour necrosis factor (TNF) α expressed by peripheral blood mononuclear cells (PBMCs) from 20 UC patient samples (Severance Hospital, Seoul, Korea). Results When VRN024219 was treated to splenocyte, the compound significantly downregulated Th17 and enhanced T reg cell differentiation. Protein levels of IL-17a, IL-6, and TNF α were increased in the DSS-induced colitis mice, whereas administration of DYRK1a inhibitor VRN024219 substantially improved clinical score than that of Tofacitinib-treated group. Additionally from T-cell transfer-induced colitis model, VRN024219 treated group demonstrated a larger population of ROR γ T-cell than that of tofacitinib Finally, the protein levels of proinflammatory cytokines were significantly down-regulated in VRN024219 treated 20 patient samples. Conclusion Our data provide clear evidence that the novel DYRK1a inhibitor plays a protective role in DSS- and T-cell transfer-induced colitis which was closely related to a Th17/Treg modulation. Thus, VRN024219 might a promising candidate for a new drug for IBD.

Circulating miRNA in atherosclerosis: a clinical biomarker and early diagnostic tool

2021 ◽  
Vol 21 ◽  
Author(s):  
Ashish Ranjan Sharma ◽  
Garima Sharma ◽  
Manojit Bhattacharya ◽  
Sang-Soo Lee ◽  
Chiranjib Chakraborty
Keyword(s):  
Arterial Wall ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Circulating Mirna ◽  
Pathological Conditions ◽  
Current Scenario ◽  
Clinical Biomarker ◽  
Diagnostic Technologies ◽  
Insight Into ◽  
Early Diagnostic

: Atherosclerosis, which is a vascular disease, is characterized by narrowing the arteries and forming plaque inside arteries. There is a record 17.5 million associated deaths recorded annually, representing 31% of global death. It has been noted that there is an association between vascular fibrosis and atherosclerosis. The thickening of the arterial wall and reduction of the lumen diameter may cause unwarranted deposition of extracellular matrix (ECM), and these conditions help in the progression of many clinical diseases and pathological conditions such as atherosclerosis. Here, we reviewed the involvement of various circulating microRNAs (miRNAs) in the very early diagnosis of atherosclerosis. We have also tried to provide an insight into the advantages and validation of circulating miRNAs through different techniques. We have discussed different circulating miRNAs, such as miR-17, miR-17-5p, miR-29b, miR-30, miR-92a, miR-126, miR-143, miR-145, miR-146a, miR-212, miR-218, miR-221, miR-222, miR-361-5p, as a biomarker for clinical diagnosis of atherosclerosis. The insightful demonstration in this review will offer a better opportunity for the researchers and technology developers in understanding the current scenario of circulating miRNA, which could facilitate them in improving the current diagnostic technologies of atherosclerosis in clinics.

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