scholarly journals Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology

2019 ◽  
Vol 115 (9) ◽  
pp. 1425-1434 ◽  
Author(s):  
Giuseppina Caligiuri
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular System ◽  
Immune Cell ◽  
Dynamic Regulation ◽  
Peripheral Tissues ◽  
Beneficial Effects ◽  
Metabolic Functions ◽  
Cellular Contact ◽  
Vascular Stiffening ◽  
Biomechanical Stimuli

Abstract Biomechanical changes in the heart and vessels drive rapid and dynamic regulation of blood flow, a vital process for meeting the changing metabolic needs of the peripheral tissues at any given point in time. The fluid movement of the blood exerts haemodynamic stress upon the solid elements of the cardiovascular system: the heart, vessels, and cellular components of the blood. Cardiovascular diseases can lead to prolonged mechanical stress, such as cardiac remodelling during heart failure or vascular stiffening in atherosclerosis. This can lead to a significantly reduced or increasingly turbulent blood supply, inducing a shift in cellular metabolism that, amongst other effects, can trigger the release of reactive oxygen species and initiate a self-perpetuating cycle of inflammation and oxidative stress. CD31 is the most abundant constitutive co-signalling receptor glycoprotein on endothelial cells, which line the cardiovascular system and form the first-line of cellular contact with the blood. By associating with most endothelial receptors involved in mechanosensing, CD31 regulates the response to biomechanical stimuli. In addition, by relocating in the lipid rafts of endothelial cells as well as of cells stably interacting with the endothelium, including leucocytes and platelets, CD31–CD31 trans-homophilic engagement guides and restrains platelet and immune cell accumulation and activation and at sites of damage. In this way, CD31 is at the centre of mediating mechanical, metabolic, and immunological changes within the circulation and provides a single target that may have pleiotropic beneficial effects.

scholarly journals Potential Cardiovascular and Metabolic Beneficial Effects of ω-3 PUFA in Male Obesity Secondary Hypogonadism Syndrome

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2519 ◽  
Author(s):  
Annalisa Noce ◽  
Giulia Marrone ◽  
Francesca Di Daniele ◽  
Manuela Di Lauro ◽  
Anna Pietroboni Zaitseva ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Composition ◽  
Polyunsaturated Fatty Acids ◽  
Cardiovascular System ◽  
Scientific Literature ◽  
Review Article ◽  
Beneficial Effects ◽  
Metabolic Functions ◽  
Secondary Hypogonadism ◽  
Long Chain

Long-chain ω-3 polyunsaturated fatty acids (PUFAs) are fundamental biocomponents of lipids and cell membranes. They are involved in the maintenance of cellular homeostasis and they are able to exert anti-inflammatory and cardioprotective actions. Thanks to their potential beneficial effects on the cardiovascular system, metabolic axis and body composition, we have examined their action in subjects affected by male obesity secondary hypogonadism (MOSH) syndrome. MOSH syndrome is characterized by the presence of obesity associated with the alteration of sexual and metabolic functions. Therefore, this review article aims to analyze scientific literature regarding the possible benefits of ω-3 PUFA administration in subjects affected by MOSH syndrome. We conclude that there are strong evidences supporting ω-3 PUFA administration and/or supplementation for the treatment and management of MOSH patients.

scholarly journals Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1855
Author(s):  
Aikaterini Gatsiou ◽  
Kateryna Sopova ◽  
Alexandros Tselepis ◽  
Konstantinos Stellos
Keyword(s):  
Endothelial Cells ◽  
Immune Cell ◽  
Vascular Endothelial Cells ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Aortic Ring ◽  
Inflammatory Factor ◽  
Vascular Endothelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Vascular Regeneration

Platelets comprise a highly interactive immune cell subset of the circulatory system traditionally known for their unique haemostatic properties. Although platelets are considered as a vault of growth factors, cytokines and chemokines with pivotal role in vascular regeneration and angiogenesis, the exact mechanisms by which they influence vascular endothelial cells (ECs) function remain underappreciated. In the present study, we examined the role of human IL-17A/IL-17RA axis in platelet-mediated pro-angiogenic responses. We reveal that IL-17A receptor (IL-17RA) mRNA is present in platelets transcriptome and a profound increase is documented on the surface of activated platelets. By quantifying the protein levels of several factors, involved in angiogenesis, we identified that IL-17A/IL17RA axis selectively induces the release of vascular endothelial growth factor, interleukin -2 and -4, as well as monocyte chemoattractant protein -1 from treated platelets. However, IL-17A exerted no effect on the release of IL-10, an anti-inflammatory factor with potentially anti-angiogenic properties, from platelets. Treatment of human endothelial cell two-dimensional tubule networks or three-dimensional spheroid and mouse aortic ring structures with IL-17A-induced platelet releasate evoked pro-angiogenic responses of ECs. Our findings suggest that IL-17A may critically affect platelet release of pro-angiogenic factors driving ECs towards a pro-angiogenic state.

scholarly journals Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 210
Author(s):  
Yanyan Wang ◽  
Yun-Ling Tai ◽  
Derrick Zhao ◽  
Yuan Zhang ◽  
Junkai Yan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Mouse Model ◽  
Disease Progression ◽  
Nonalcoholic Steatohepatitis ◽  
Noncoding Rna ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Stellate Cell ◽  
Clinical Investigation ◽  
Beneficial Effects

Background and Aims: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and has various beneficial effects on metabolic diseases, including NAFLD/NASH. However, the underlying mechanisms remain incompletely understood due to the limitation of the NASH animal models used. Methods: A high-fat and high-fructose diet-induced mouse model of NAFLD, the best available preclinical NASH mouse model, was used. RNAseq, histological, and metabolic pathway analyses were used to identify the potential signaling pathways modulated by BBR. LC–MS was used to measure bile acid levels in the serum and liver. The real-time RT-PCR and Western blot analysis were used to validate the RNAseq data. Results: BBR not only significantly reduced hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also restored the bile acid homeostasis by targeting multiple pathways. In addition, BBR markedly inhibited inflammation by reducing immune cell infiltration and inhibition of neutrophil activation and inflammatory gene expression. Furthermore, BBR was able to inhibit hepatic fibrosis by modulating the expression of multiple genes involved in hepatic stellate cell activation and cholangiocyte proliferation. Consistent with our previous findings, BBR’s beneficial effects are linked with the downregulation of microRNA34a and long noncoding RNA H19, which are two important players in promoting NASH progression and liver fibrosis. Conclusion: BBR is a promising therapeutic agent for NASH by targeting multiple pathways. These results provide a strong foundation for a future clinical investigation.

Endothelial Cell-Immune Cell Interaction in IBD

2016 ◽  
Vol 34 (1-2) ◽  
pp. 43-50 ◽  
Author(s):  
Silvio Danese ◽  
Claudio Fiocchi
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Bowel Wall ◽  
Regulatory Mechanism ◽  
Immune Cell ◽  
Cell Interaction ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Inflammatory Bowel ◽  
Lymphatic Fluid

The proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid. The disruption of any of the above regulatory mechanism can lead to inflammation, as is the case for inflammatory bowel disease. Learning how leukocyte and endothelial cells mutually function in health and what goes wrong in inflammation offers the opportunity to intervene therapeutically and re-establish the normal crosstalk between leukocytes and endothelial cells.

scholarly journals Endothelial insulin receptors differentially control insulin signaling kinetics in peripheral tissues and brain of mice

2017 ◽  
Vol 114 (40) ◽  
pp. E8478-E8487 ◽  
Author(s):  
Masahiro Konishi ◽  
Masaji Sakaguchi ◽  
Samuel M. Lockhart ◽  
Weikang Cai ◽  
Mengyao Ella Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Cells ◽  
Food Intake ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Insulin Receptors ◽  
Brain Regions ◽  
Peripheral Tissues ◽  
Systemic Insulin Resistance

Insulin receptors (IRs) on endothelial cells may have a role in the regulation of transport of circulating insulin to its target tissues; however, how this impacts on insulin action in vivo is unclear. Using mice with endothelial-specific inactivation of the IR gene (EndoIRKO), we find that in response to systemic insulin stimulation, loss of endothelial IRs caused delayed onset of insulin signaling in skeletal muscle, brown fat, hypothalamus, hippocampus, and prefrontal cortex but not in liver or olfactory bulb. At the level of the brain, the delay of insulin signaling was associated with decreased levels of hypothalamic proopiomelanocortin, leading to increased food intake and obesity accompanied with hyperinsulinemia and hyperleptinemia. The loss of endothelial IRs also resulted in a delay in the acute hypoglycemic effect of systemic insulin administration and impaired glucose tolerance. In high-fat diet-treated mice, knockout of the endothelial IRs accelerated development of systemic insulin resistance but not food intake and obesity. Thus, IRs on endothelial cells have an important role in transendothelial insulin delivery in vivo which differentially regulates the kinetics of insulin signaling and insulin action in peripheral target tissues and different brain regions. Loss of this function predisposes animals to systemic insulin resistance, overeating, and obesity.

Abstract 427: Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) Provides Beneficial Effects Post-MI by Promoting Angiogenesis

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Abhijit R Takawale ◽  
Pu Zhang ◽  
Ratnadeep Basu ◽  
Abul Azad ◽  
Maikel Farhan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Left Ventricular ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Lv Function ◽  
Vascular Density ◽  
Tissue Inhibitor ◽  
Infarct Zone ◽  
Fibrin Gel ◽  
Beneficial Effects

Introduction: Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) remodelling, leading to left ventricular (LV) dilation and dysfunction. Tissue inhibitor of metalloproteinase (TIMPs) are MMP inhibitors, main regulators of ECM integrity. TIMPs can also regulate other aspects of myocardial remodeling such as hypertrophy, fibrosis and inflammation. TIMP3 levels are reduced in the peri-infarct zone within 24 hours post-MI in mice. Hypothesis: Replenishment of TIMP3 post-MI limit infarct expansion, and attenuate LV dilation and dysfunction. Methods: MI was induced in adult male wildtype (C57BL/6) mice by ligation of the left anterior descending artery. Adenoviral constructs expressing human TIMP3 (Ad- hTIMP3) or no-TIMP (Ad-Null, control) were injected in the peri-infarct zone (5.4x10 7 pfu, 5 injections/heart). Cardiac function was assessed by echocardiography. Cardiomyocyte density (WGA/DAPI staining), vascular density (Fluo-lectin injection, CD31 IHC), ECM composition (PSR staining) were assessed at 3 and 7 days post-MI. In vitro, angiogenic potency of TIMP3 (rTIMP3) was assessed using the 3D fibrin gel-based angiogenesis assay using primary human vascular (HUVECs) and coronary artery endothelial cells (HCAECs), and co-IP between TIMP3 and VEGFR2. Results: Ad-TIMP3 injections significantly improved LV function and reduced LV dilation as compared to Ad-Null group post-MI. Infarct size was markedly reduced with TIMP3 injections and more viable myocytes were preserved in the infarct zone at 1wk post-MI. Ad-TIMP3-MI group showed a higher density of endothelial cells and increased coronary density in the infarct and peri-infarct regions compared to the Ad-null group. This suggested that Ad-TIMP3 promotes angiogenesis in the infarcted myocardium. In vitro studies confirmed that rTIMP3 promoted angiogenesis/sprouting in human endothelial cells up to100ng/ml. However at higher concentrations (>1ug/ml), rTIMP3 exerted anti-angiogenic effects by binding to VEGFR2. This function of rTIMP3 appears to be through an MMP-inhibitory mechanism. Conclusion: The novel pro-angiogenic function of TIMP3 post-MI could provide additional beneficial effects in post-MI treatment.

Translational research of hemoglobin vesicles as a transfusion alternative

2021 ◽  
Vol 28 ◽  
Author(s):  
Hiromi Sakai ◽  
Naoko Kobayashi ◽  
Tomoko Kure ◽  
Chie Okuda
Keyword(s):  
Blood Donation ◽  
Biologic Agent ◽  
Oxygen Carriers ◽  
Peripheral Tissues ◽  
Beneficial Effects ◽  
Phenothiazine Dyes ◽  
Artificial Oxygen Carriers ◽  
Donated Blood ◽  
Electron Mediators ◽  
Anti Inflammation

: Clinical situations arise in which blood for transfusion becomes scarce or unavailable. Considerable demand for a transfusion alternative persists because of various difficulties posed by blood donation and transfusion systems. Hemoglobin-vesicles (HbV) are artificial oxygen carriers being developed for use as a transfusion alternative. Just as biomembranes of red blood cells (RBCs) do, phospholipid vesicles (liposomes) for Hb encapsulation can protect the human body from toxic effects of molecular Hb. The main HbV component, Hb, is obtained from discarded human donated blood. Therefore, HbV can be categorized as a biologic agent targeting oxygen for peripheral tissues. The purification procedure strictly eliminates the possibility of viral contamination. It also removes all concomitant unstable enzymes present in RBC for utmost safety from infection. The deoxygenated HbVs, which are storable for over years at ambient temperature, can function as an alternative to blood transfusion for resuscitation from hemorrhagic shock and O2 therapeutics. Moreover, a recent study clarified beneficial effects for anti-oxidation and anti-inflammation by carbon monoxide (CO)-bound HbVs. Autoxidation of HbV (HbO2 → metHb + O2-.) is unavoidable after intravenous administration. Co-injection of methylene blue can extract the intraerythrocytic glycolytic electron energy effectively and reduce metHb. Other phenothiazine dyes can also function as electron mediators to improve the functional life span of HbV. This review paper summarizes recent progress of the research and development of HbV, aimed at clinical applications.

Abstract 1746: Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Mediates Vascular Repair By HDL Receptor Activation And Sphingosine Kinase (SK-1)/Sphingosine 1-Phosphate (S1P) Dependent Nitric Oxide (NO) Generation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Sergio Li Calzi ◽  
Jennifer L Kielczewski ◽  
Evan McFarland ◽  
Kyung Hee Chang ◽  
Aqeela Afzal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Scavenger Receptor ◽  
Receptor Activation ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Sphingosine 1 Phosphate ◽  
Active Motor ◽  
Umbilical Vein Endothelial Cells ◽  
Igfbp 3

Purpose: We demonstrated that IGFBP-3 stimulates hematopoietic stem cells (HSC) to differentiate into endothelial cells, form capillaries, and stabilize the vasculature (Chang, et al, PNAS 2007). Local IGFBP- 3 production is increased by hypoxia and facilitates the homing of HSC to areas of injury. In the circulation, IGFBP-3 is bound to HDL. In this study, we investigated the signaling pathways responsible for the robust migratory effects of IGFBP-3. Methods: The effects of IGFBP-3 on NO generation in human vascular precursors (CD 34 + , CD14 − ), human lung microvascular endothelial cells, and human umbilical vein endothelial cells were examined using DAF-FM fluorescence. Western analysis was use for detection of eNOS and vasodilator-stimulated phosphoprotein (VASP), which redistributes to lamellipodia forming an active motor complex that supports motility and is phosphorylated in response to NO. Localization of VASP was performed by immunohistochemistry. SK-1 was assessed following IGFBP-3 stimulation. Results: In CD34 + cells and endothelial cells, IGFBP-3 stimulated eNOS phosphorylation at Ser1177 (102 ± 1.8%, P = 0.0002) and increased NO generation (275 ± 50%, P = 0.05) by increasing SK-1 and S1P generation. IGFBP-3 was bound and internalized by the HDL receptor, scavenger receptor 1B (SR1B). NO generation following IGFBP-3 exposure was reduced by SK inhibitors or SR-1B blocking antibody pretreatment (35 ± 5%, P < 0.02). IGFBP-3 generated NO increased phosphorylation of VASP at Ser239 and promoted the redistribution of VASP to lamellipodia. Conclusions: IGFBP-3 effects on cell migration are NO dependent and mediated in part by activation of the HDL receptor SR1B suggesting that some of the beneficial effects of HDL are mediated by the association of IGFBP-3.

scholarly journals Hepatic functions of GLP-1 and its based drugs: current disputes and perspectives

2016 ◽  
Vol 311 (3) ◽  
pp. E620-E627 ◽  
Author(s):  
Tianru Jin ◽  
Jianping Weng
Keyword(s):  
Insulin Resistance ◽  
Degradation Products ◽  
Hepatic Glucose Production ◽  
Wnt Signaling Pathway ◽  
Glucose Production ◽  
Metabolic Effects ◽  
Beneficial Effects ◽  
Metabolic Functions ◽  
Pathway Activation ◽  
Hepatic Glucose

GLP-1 and its based drugs possess extrapancreatic metabolic functions, including that in the liver. These direct hepatic metabolic functions explain their therapeutic efficiency for subjects with insulin resistance. The direct hepatic functions could be mediated by previously assumed “degradation” products of GLP-1 without involving canonic GLP-1R. Although GLP-1 analogs were created as therapeutic incretins, extrapancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important. Postprandial GLP-1 release contributes to insulin secretion, which represses hepatic glucose production. This indirect effect of GLP-1 is known as the gut-pancreas-liver axis. Great efforts have been made to determine whether GLP-1 and its analogs possess direct metabolic effects on the liver, as the determination of the existence of direct hepatic effects may advance the therapeutic theory and clinical practice on subjects with insulin resistance. Furthermore, recent investigations on the metabolic beneficial effects of previously assumed “degradation” products of GLP-1 in the liver and elsewhere, including GLP-128–36 and GLP-132–36, have drawn intensive attention. Such investigations may further improve the development and the usage of GLP-1-based drugs. Here, we have reviewed the current advancement and the existing controversies on the exploration of direct hepatic functions of GLP-1 and presented our perspectives that the direct hepatic metabolic effects of GLP-1 could be a GLP-1 receptor-independent event involving Wnt signaling pathway activation.

Sign in / Sign up

Export Citation Format

Share Document