scholarly journals Thrombo-Inflammation: A Focus on NTPDase1/CD39

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2223
Author(s):  
Silvana Morello ◽  
Elisabetta Caiazzo ◽  
Roberta Turiello ◽  
Carla Cicala
Keyword(s):  
Blood Flow ◽  
Blood Loss ◽  
Vascular Endothelium ◽  
Tissue Injury ◽  
Endothelial Damage ◽  
Dense Granules ◽  
Injured Tissue ◽  
Activated Platelets ◽  
Altered Blood

There is increasing evidence for a link between inflammation and thrombosis. Following tissue injury, vascular endothelium becomes activated, losing its antithrombotic properties whereas inflammatory mediators build up a prothrombotic environment. Platelets are the first elements to be activated following endothelial damage; they participate in physiological haemostasis, but also in inflammatory and thrombotic events occurring in an injured tissue. While physiological haemostasis develops rapidly to prevent excessive blood loss in the endothelium activated by inflammation, hypoxia or by altered blood flow, thrombosis develops slowly. Activated platelets release the content of their granules, including ATP and ADP released from their dense granules. Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 dephosphorylates ATP to ADP and to AMP, which in turn, is hydrolysed to adenosine by ecto-5′-nucleotidase (CD73). NTPDase1/CD39 has emerged has an important molecule in the vasculature and on platelet surfaces; it limits thrombotic events and contributes to maintain the antithrombotic properties of endothelium. The aim of the present review is to provide an overview of platelets as cellular elements interfacing haemostasis and inflammation, with a particular focus on the emerging role of NTPDase1/CD39 in controlling both processes.

Role of Altered Blood Properties in the Propagation of Ischemic Blood Flow: Contribution of Aging and Oxidative Stress

2001 ◽  
pp. 369-380 ◽  
Author(s):  
Joseph M. Rifkind ◽  
Omoefe O. Abugo ◽  
Enika Nagababu ◽  
Ranjeet S. Ajmani ◽  
E. Jeffrey Metter ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Altered Blood ◽  
And Oxidative Stress

scholarly journals Intercellular Conduction Optimizes Arterial Network Function and Conserves Blood Flow Homeostasis during Cerebrovascular Challenges

2019 ◽  
Author(s):  
Anil Zechariah ◽  
Cam Ha T. Tran ◽  
Bjorn O. Hald ◽  
Shaun L. Sandow ◽  
Maria Sancho ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tissue Injury ◽  
Vascular Cells ◽  
Arterial Tree ◽  
Gap Junctional Communication ◽  
Arterial Network ◽  
Junctional Communication ◽  
Electrical Signalling ◽  
Gap Junctional

AbstractCerebral arterial networks match blood flow delivery with neural activity. Neurovascular response begins with a stimulus and a focal change in vessel diameter, which by themselves is inconsequential to blood flow magnitude, until they spread and alter the contractile status of neighboring arterial segments. We sought to define the mechanisms underlying integrated vascular behavior and considered the role of intercellular electrical signalling in this phenomenon. Electron microscopic and histochemical analysis revealed the structural coupling of cerebrovascular cells and the expression of gap junctional subunits at the cell interfaces, enabling intercellular signaling among vascular cells. Indeed, robust vasomotor conduction was detected in human and mice cerebral arteries after focal vessel stimulation; a response attributed to endothelial gap junctional communication, as its genetic alteration attenuated this behavior. Conducted responses was observed to ascend from the penetrating arterioles, influencing the contractile status of cortical surface vessels, in a simulated model of cerebral arterial network. Ascending responses recognised in vivo after whisker stimulation, were significantly attenuated in mice with altered endothelial gap junctional signalling confirming that gap junctional communication drives integrated vessel responses. The diminishment in vascular communication also impaired the critical ability of the cerebral vasculature to maintain blood flow homeostasis and hence tissue viability, after stroke. Our findings establish the integral role of intercellular electrical signalling in transcribing focal stimuli into coordinated changes in cerebrovascular contractile activity and expose, a hitherto unknown mechanism for flow regulation after stroke.SignificanceNeurovascular responses are viewed as a one step process whereby stimuli derived from neural cells focally diffuse to a neighboring vessel, altering its contractile state. While focal changes in tone can subtly tune flow distribution, they can’t substantively change “perfusion magnitude” as vascular resistance is broadly distributed along the cerebral arterial tree. We report that nature overcomes this biophysical constraint by conducting electrical signals among coupled vascular cells, along vessels, and across branch points. Our quantitative exploration of intercellular conduction illustrates how network coordination optimizes blood flow delivery in support of brain function. Diminishing the ability of vascular cells to electrically communicate, mitigates the brain’s ability to regulate perfusion during functional hyperemia and after stroke, the latter advancing tissue injury.

CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen

2005 ◽  
Vol 93 (02) ◽  
pp. 311-318 ◽  
Author(s):  
Eileen McMillan-Ward ◽  
Sara Israels
Keyword(s):  
Tyrosine Phosphorylation ◽  
Confocal Imaging ◽  
Dependent Manner ◽  
Lipid Kinase ◽  
Actin Reorganization ◽  
Dense Granules ◽  
Activated Platelets ◽  
And Migration ◽  
Platelet Spreading

SummaryCD63 is a member of the tetraspanin superfamily of integral membrane proteins. Present on a variety of cells, tetraspanins can form lateral associations with integrins and may act as ‘organizers’ of multimolecular networks that modulate integrinmediated signaling, cell morphology, motility and migration. In resting platelets, CD63 is present on the membranes of dense granules and lysosomes but relocates to the plasma membrane following platelet activation and exocytosis where it associates with the platelet integrin α IIbβ 3-CD9 complex and with the actin cytoskeleton in an α IIbβ 3-dependent manner. D545, a monoclonal antibody directed at the second extracellular loop of CD63,was used to investigate the role of CD63 in platelet adhesion, spreading and tyrosine phosphorylation. Using immunofluorescence microscopy and confocal imaging, we have demonstrated that D545 does not alter adhesion of platelets to immobilized fibrinogen, but instead platelet spreading. In the presence of buffer or non-specific mouse IgG, activated platelets showed fully spread morphology, F-actin reorganization, redistribution of vinculin and extensive tyrosine phosphorylation, all of which were inhibited by D545. D545 also inhibited the phosphorylation of focal adhesion kinase in thrombin-activated adherent platelets. These results suggest that CD63 may modulate α IIbβ 3-dependent cytoskeletal reorganization. To identify signaling enzymes associated with CD63 that could affect this pathway, lipid kinase assays were performed on D545 immunoprecipitates. CD63 co-immunoprecipitated with a lipid kinase which, on the basis of enzymatic properties(stimulated by nonionic detergents, inhibited by adenosine), is consistent with PI 4-kinase type II. The CD63-PI 4-kinase complex was not activation- dependent as the constituents were co-purified from both resting and activated platelets. The linkage of CD63 with PI 4-kinase may result in the recruitment of this signaling enzyme to specific membrane locations in the platelet where it influences phosphoinositide-dependent signaling and platelet spreading.

scholarly journals Adipocyte-Endothelium Crosstalk in Obesity

2021 ◽  
Vol 12 ◽  
Author(s):  
Rugivan Sabaratnam ◽  
Per Svenningsen
Keyword(s):  
Metabolic Disease ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelium ◽  
Energy Homeostasis ◽  
Cell Communication ◽  
Normal Organ ◽  
Arterial Endothelial Cells

Obesity is characterized by pathological adipose tissue (AT) expansion. While healthy AT expansion enhances systemic insulin sensitivity, unhealthy AT expansion through increased adipocyte size is associated with insulin resistance, fibrosis, hypoxia, and reduced adipose-derived adiponectin secretion. The mechanisms causing the unhealthy AT expansion are not fully elucidated; yet, dysregulated crosstalk between cells within the AT is an important contributor. Evidence from animal and human studies suggests a crucial role of the crosstalk between vascular endothelium (the innermost cell type in blood vessels) and adipocytes for metabolic homeostasis. Arterial endothelial cells are directly involved in maintaining normal organ functions through local blood flow regulation. The endothelial-dependent regulation of blood flow in AT is hampered in obesity, which negatively affects the adipocyte. Moreover, endothelial cells secrete extracellular vesicles (EVs) that target adipocytes in vivo. The endothelial EVs secretion is hampered in obesity and may be affected by the adipocyte-derived adipokine adiponectin. Adiponectin targets the vascular endothelium, eliciting organ-protective functions through binding to T-cadherin. The reduced obesity-induced adiponectin binding of T-cadherin reduces endothelial EV secretion. This affects endothelial health and cell-cell communication between AT cells and distant organs, influencing systemic energy homeostasis. This review focuses on the current understanding of endothelial and adipocyte crosstalk. We will discuss how obesity changes the AT environment and how these changes contribute to obesity-associated metabolic disease in humans. Particularly, we will describe and discuss the EV-dependent communication and regulation between adipocytes, adiponectin, and the endothelial cells regulating systemic energy homeostasis in health and metabolic disease in humans.

scholarly journals The Role of Cutaneous Microcirculatory Responses in Tissue Injury, Inflammation and Repair at the Foot in Diabetes

2021 ◽  
Vol 9 ◽  
Author(s):  
Gayathri Victoria Balasubramanian ◽  
Nachiappan Chockalingam ◽  
Roozbeh Naemi
Keyword(s):  
Blood Flow ◽  
Soft Tissue ◽  
Diabetic Foot ◽  
Soft Tissues ◽  
Tissue Injury ◽  
Applied Pressure ◽  
Skin Perfusion ◽  
Increased Risk ◽  
Microcirculatory Function

Diabetic foot syndrome is one of the most costly complications of diabetes. Damage to the soft tissue structure is one of the primary causes of diabetic foot ulcers and most of the current literature focuses on factors such as neuropathy and excessive load. Although the role of blood supply has been reported in the context of macro-circulation, soft tissue damage and its healing in the context of skin microcirculation have not been adequately investigated. Previous research suggested that certain microcirculatory responses protect the skin and their impairment may contribute to increased risk for occlusive and ischemic injuries to the foot. The purpose of this narrative review was to explore and establish the possible link between impairment in skin perfusion and the chain of events that leads to ulceration, considering the interaction with other more established ulceration factors. This review highlights some of the key skin microcirculatory functions in response to various stimuli. The microcirculatory responses observed in the form of altered skin blood flow are divided into three categories based on the type of stimuli including occlusion, pressure and temperature. Studies on the three categories were reviewed including: the microcirculatory response to occlusive ischemia or Post-Occlusive Reactive Hyperaemia (PORH); the microcirculatory response to locally applied pressure such as Pressure-Induced Vasodilation (PIV); and the interplay between microcirculation and skin temperature and the microcirculatory responses to thermal stimuli such as reduced/increased blood flow due to cooling/heating. This review highlights how microcirculatory responses protect the skin and the plantar soft tissues and their plausible dysfunction in people with diabetes. Whilst discussing the link between impairment in skin perfusion as a result of altered microcirculatory response, the review describes the chain of events that leads to ulceration. A thorough understanding of the microcirculatory function and its impaired reactive mechanisms is provided, which allows an understanding of the interaction between functional disturbances of microcirculation and other more established factors for foot ulceration.

scholarly journals The Role of the Signaling Pathways Involved in the Protective Effect of Exogenous Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuangyu Lv ◽  
Xiaotian Li ◽  
Shizhen Zhao ◽  
Huiyang Liu ◽  
Honggang Wang
Keyword(s):  
Blood Flow ◽  
Hydrogen Sulfide ◽  
Signaling Pathways ◽  
Structural Changes ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Cell Swelling ◽  
Signal Pathways

Ischemia/reperfusion (I/R) injury refers to the functional and structural changes in the process of blood flow recovery after ischemia. In addition to ischemia, the blood flow recovery can also lead to very harmful damage, such as the obvious cell swelling and the irreversible cell necrosis. I/R injury is related with many diseases, including myocardial I/R injury. Myocardial I/R injury refers to the aggravation of ischemic myocardial tissue injury due to sudden disorder of blood circulation. Although there are many studies on myocardial I/R injury, the exact mechanism is not fully understood. Hydrogen sulfide (H2S), like carbon monoxide and nitric oxide, is an important gas signal molecule. It plays an important role in many physiological and pathological processes. Recent studies indicate that H2S can improve myocardial I/R injury, however, its mechanism is not fully understood, especially the involved signal pathways. In this review, we summarize the related researches about the role of the signaling pathways involved in the protective effects of exogenous H2S on myocardial I/R injury, so as to provide theoretical reference for the future in-depth researches.

Vasopressin and fetal cerebrovascular regulation

1992 ◽  
Vol 263 (2) ◽  
pp. R376-R381
Author(s):  
J. C. Eisenach ◽  
C. Tong ◽  
D. A. Stump ◽  
S. M. Block
Keyword(s):  
Blood Flow ◽  
Vascular Endothelium ◽  
Dependent Manner ◽  
Independent Manner ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Cerebrovascular Regulation ◽  
Indomethacin Treatment

Vasopressin (AVP) may increase cerebral blood flow (CBF) during hypoxemia by selective dilatation of cerebral vessels via endothelium-derived relaxing factor (EDRF) release. To test whether this action is relevant in the fetus, we produced isocapnic hypoxemia in halothane-anesthetized pregnant ewes. Fetal infusion of a V1 AVP antagonist reduced by 55% the increase in CBF during fetal hypoxemia. To test the role of this response during development, we examined the response to AVP in intact and endothelium-denuded femoral and basilar arterial rings in vitro from fetal, newborn, and adult sheep. AVP constricted femoral rings in an endothelium-independent manner, with increased potency in newborn and fetal compared with adult rings. AVP relaxed basilar rings in an endothelium-dependent manner, which was unaffected by indomethacin treatment, with increased potency in newborn and adult compared with fetal rings. We conclude that fetal cerebral vascular endothelium is functional and responsive to AVP and that circulating AVP during fetal hypoxemia contributes to increased CBF via this effect.

Sign in / Sign up

Export Citation Format

Share Document