scholarly journals VASP regulates leukocyte infiltration, polarization, and vascular repair after ischemia

2018 ◽  
Vol 217 (4) ◽  
pp. 1503-1519 ◽  
Author(s):  
Hebatullah Laban ◽  
Andreas Weigert ◽  
Joana Zink ◽  
Amro Elgheznawy ◽  
Christoph Schürmann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Chemokine Receptor ◽  
Vascular Diseases ◽  
Leukocyte Recruitment ◽  
Receptor Internalization ◽  
Leukocyte Infiltration ◽  
Vascular Repair ◽  
Bone Marrow Derived Cells ◽  
Increased Blood Flow

In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP−/− mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair. Importantly, VASP deletion in bone marrow–derived cells was sufficient to mimic the increased blood flow recovery of global VASP−/− mice. In chemotaxis experiments, VASP−/− neutrophils/monocytes were significantly more responsive to M1-related chemokines than wild-type controls. Mechanistically, VASP formed complexes with the chemokine receptor CCR2 and β-arrestin-2, and CCR2 receptor internalization was significantly reduced in VASP−/− leukocytes. Our data indicate that VASP is a major regulator of leukocyte recruitment and polarization in postischemic revascularization and support a novel role of VASP in chemokine receptor trafficking.

Role of adenosine in postprandial and reactive hyperemia in canine jejunum

1992 ◽  
Vol 263 (4) ◽  
pp. G487-G493 ◽  
Author(s):  
D. R. Sawmiller ◽  
C. C. Chou
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Adenosine Deaminase ◽  
Reactive Hyperemia ◽  
Concentration Difference ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
Increased Blood Flow

The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum.

Abstract P141: GYY4137, a H 2 S Donor, Normalizes miR-132 Targeted Sirt1 and Ace2 Expression to Improve Kidney Function in Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Gregory Weber ◽  
Sathnur Pushpakumar ◽  
Utpal Sen
Keyword(s):  
Blood Flow ◽  
Kidney Function ◽  
Expression Patterns ◽  
Sirtuin 1 ◽  
Ang Ii ◽  
Cellular Processes ◽  
Physiological Processes ◽  
Epigenetic Gene Silencing ◽  
Increased Blood Flow

MicroRNAs regulate several physiological processes and are implicated in various pathologies, including hypertension. Previous work indicates miR-132 targets Sirtuin 1 (Sirt1), a histone deacetylase and regulator of epigenetic gene silencing in various cellular processes. Sirt1 is expressed in the kidney; however, its role in hypertensive kidney and whether it is regulated by physiological gaseous molecules, such as hydrogen sulfide (H 2 S), is not known. In this study, we sought to determine the role of miR-132 in regulating Sirt1, Ace2 and At1 in hypertensive kidney and whether H 2 S donor, GYY4137 (GYY), could reverse these effects and mitigates renal dysfunction. Wild-type mice were treated without or with Ang-II (1000 ng/Kg/Min) and GYY (133 μM) for 4 weeks. Quantitative PCR, Western blot, and immunofluorescence assays were performed. Increased expression levels of miR-132 in hypertensive mice (3.79 fold vs control) were reduced in mice receiving GYY treatment (2.43 fold vs control). Sirt1 expression was reduced (-1.15 fold) in Ang-II mice but was upregulated in GYY (1.25 fold) and Ang-II+GYY (1.9 fold) groups. A similar effect was seen with Sirt1 protein where the expression was increased in animals treated with GYY and Ang-II+GYY (1.16, 1.03 respectively) compared to Ang-II (0.47). Ace2 in Ang-II+GYY (0.45) was increased compared to Ang-II (0.17), while At1 was reduced (0.46) compared to Ang-II (0.86). Immunofluorescence showed decreased signal of Sirt1 in the glomerulus in Ang-II mice and increased At1 in the blood vessels surrounding the glomerulus, leading to constriction of renal artery, decreased blood flow, and kidney dysfunction. These effects were alleviated in mice treated with GYY. Our data suggests that upregulation of miR-132 in hypertensive kidney decreases Sirt1 and Ace2 expression, leading to increased Ang-II signaling through the At1 receptor and GYY supplementation reverses these expression patterns, leading to increased blood flow and kidney function.

scholarly journals The role of oxygen transport in atherosclerosis and vascular disease

2020 ◽  
Vol 17 (165) ◽  
pp. 20190732 ◽  
Author(s):  
John Tarbell ◽  
Marwa Mahmoud ◽  
Andrea Corti ◽  
Luis Cardoso ◽  
Colin Caro
Keyword(s):  
Blood Flow ◽  
Vascular Disease ◽  
Oxygen Transport ◽  
Intimal Hyperplasia ◽  
Hypoxia Inducible Factor ◽  
Vascular Diseases ◽  
Vascular Wall ◽  
Vasa Vasorum ◽  
Mechanical Factors

Atherosclerosis and vascular disease of larger arteries are often associated with hypoxia within the layers of the vascular wall. In this review, we begin with a brief overview of the molecular changes in vascular cells associated with hypoxia and then emphasize the transport mechanisms that bring oxygen to cells within the vascular wall. We focus on fluid mechanical factors that control oxygen transport from lumenal blood flow to the intima and inner media layers of the artery, and solid mechanical factors that influence oxygen transport to the adventitia and outer media via the wall's microvascular system—the vasa vasorum (VV). Many cardiovascular risk factors are associated with VV compression that reduces VV perfusion and oxygenation. Dysfunctional VV neovascularization in response to hypoxia contributes to plaque inflammation and growth. Disturbed blood flow in vascular bifurcations and curvatures leads to reduced oxygen transport from blood to the inner layers of the wall and contributes to the development of atherosclerotic plaques in these regions. Recent studies have shown that hypoxia-inducible factor-1α (HIF-1α), a critical transcription factor associated with hypoxia, is also activated in disturbed flow by a mechanism that is independent of hypoxia. A final section of the review emphasizes hypoxia in vascular stenting that is used to enlarge vessels occluded by plaques. Stenting can compress the VV leading to hypoxia and associated intimal hyperplasia. To enhance oxygen transport during stenting, new stent designs with helical centrelines have been developed to increase blood phase oxygen transport rates and reduce intimal hyperplasia. Further study of the mechanisms controlling hypoxia in the artery wall may contribute to the development of therapeutic strategies for vascular diseases.

scholarly journals β2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury

2016 ◽  
Vol 113 (52) ◽  
pp. 15126-15131 ◽  
Author(s):  
Laurel A. Grisanti ◽  
Christopher J. Traynham ◽  
Ashley A. Repas ◽  
Erhe Gao ◽  
Walter J. Koch ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Immune Cell ◽  
Critical Role ◽  
Cardiac Injury ◽  
Leukocyte Recruitment ◽  
Acute Injury ◽  
Leukocyte Infiltration ◽  
Activator Protein 1 ◽  
Ccr2 Expression

Following cardiac injury, early immune cell responses are essential for initiating cardiac remodeling and tissue repair. We previously demonstrated the importance of β2-adrenergic receptors (β2ARs) in the regulation of immune cell localization following acute cardiac injury, with deficient leukocyte infiltration into the damaged heart. The purpose of this study was to investigate the mechanism by which immune cell-expressed β2ARs regulate leukocyte recruitment to the heart following acute cardiac injury. Chemokine receptor 2 (CCR2) expression and responsiveness to C-C motif chemokine ligand 2 (CCL2)-mediated migration were abolished in β2AR knockout (KO) bone marrow (BM), both of which were rescued by β2AR reexpression. Chimeric mice lacking immune cell-specific CCR2 expression, as well as wild-type mice administered a CCR2 antagonist, recapitulated the loss of monocyte/macrophage and neutrophil recruitment to the heart following myocardial infarction (MI) observed in mice with immune cell-specific β2AR deletion. Converse to β2AR ablation, β2AR stimulation increased CCR2 expression and migratory responsiveness to CCL2 in BM. Mechanistically, G protein-dependent β2AR signaling was dispensable for these effects, whereas β-arrestin2–biased β2AR signaling was required for the regulation of CCR2 expression. Additionally, activator protein 1 (AP-1) was shown to be essential in mediating CCR2 expression in response to β2AR stimulation in both murine BM and human monocytes. Finally, reconstitution of β2ARKO BM with rescued expression of a β-arrestin–biased β2AR in vivo restored BM CCR2 expression as well as cardiac leukocyte infiltration following MI. These results demonstrate the critical role of β-arrestin2/AP-1–dependent β2AR signaling in the regulation of CCR2 expression and recruitment of leukocytes to the heart following injury.

Effect of atriopeptin on blood flow to cerebrum and choroid plexus

1989 ◽  
Vol 257 (6) ◽  
pp. R1365-R1369
Author(s):  
K. A. Schalk ◽  
J. L. Williams ◽  
D. D. Heistad
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Choroid Plexus ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Increased Blood Flow

The goal of this study was to determine whether atriopeptin alters blood flow to cerebrum and choroid plexus. In anesthetized rabbits, blood flow (microspheres) to cerebrum and choroid plexus under control conditions was 36 +/- 3 (mean +/- SE) and 573 +/- 78 ml.min-1.100 g-1, respectively. Infusion of atriopeptin (75, 225, 1,150 ng.kg-1.min-1 iv) increased blood flow to choroid plexus by 22 +/- 11, 53 +/- 26, and 51 +/- 13%, respectively. In contrast, blood flow to cerebrum was not altered by atriopeptin, presumably because the blood-brain barrier prevented access to cerebral vascular smooth muscle. Because a major role of atriopeptin may be to modulate responses to angiotensin II, we examined effects of atriopeptin on vasoconstrictor responses to angiotensin II in the choroid plexus. Angiotensin II was infused in the presence or absence of atriopeptin (300 ng.kg-1.min-1 iv). Angiotensin II (100 ng.kg-1.min-1 iv) decreased blood flow to choroid plexus by 49 +/- 12% and by 47 +/- 14% during simultaneous infusion of atriopeptin. In summary, atriopeptin 1) increases blood flow to choroid plexus, but not cerebrum, and 2) does not appear to attenuate vasoconstrictor effects of angiotensin II in the choroid plexus.

Role of endothelial factors in active hyperemic responses in contracting canine muscle

1995 ◽  
Vol 79 (1) ◽  
pp. 107-112 ◽  
Author(s):  
C. E. King-Vanvlack ◽  
S. E. Curtis ◽  
J. D. Mewburn ◽  
S. M. Cain ◽  
C. K. Chapler
Keyword(s):  
Blood Flow ◽  
Gastrocnemius Muscle ◽  
Force Transducer ◽  
Tension Development ◽  
Relaxing Factor ◽  
Inhibit Prostaglandin Synthesis ◽  
Anesthetized Dogs ◽  
Endothelium Derived Relaxing Factor ◽  
Increased Blood Flow

We investigated whether endothelium-derived relaxing factor (EDRF) and prostaglandins, which may be released under conditions of increased blood flow, contribute to the active hyperemia in contracting muscle of anesthetized dogs. The venous outflow from the left gastrocnemius muscle was isolated and measured. The tendon was cut and placed in a force transducer. One group served as a control (Con; n = 9); EDRF synthesis was inhibited using N omega-nitro-L-arginine methyl ester (L-NAME) in a second group (n = 9), and a third group (n = 7) received L-NAME and indomethacin (L-NAME+Indo) to inhibit prostaglandin synthesis. After resting measurements, the distal end of the cut sciatic nerve was stimulated to produce isometric contractions at 1, 2, 4, and 6 twitches/s for 6–8 min, separated by 25-min recovery periods. Blood flow and O2 uptake increased linearly from resting values of 11.8 +/- 2.4 and 0.3 +/- 0.05 ml.100 g-1.min-1, respectively, to maximal values of 84.2 +/- 5.1 and 11.1 +/- 0.7 ml.100 g-1.min-1 in the Con group; neither these values nor those for tension development were different from values observed at comparable contraction frequencies in the L-NAME and L-NAME+Indo groups. At rest, resistance was greater (P < 0.05) in both the L-NAME and L-NAME+Indo groups compared with Con, the highest value (P < 0.05) occurring in the L-NAME+Indo group. Muscle resistance decreased (P < 0.05) in all groups at all contraction frequencies; the values were not different among the three groups.

scholarly journals Role of the Cervical Anterior Spinal Artery in the Endovascular Treatment of Vascular Diseases: Bystander, Accomplice, Victim, or Friend?

2021 ◽  
Vol 12 ◽  
Author(s):  
Kun Zhang ◽  
Chao Li ◽  
Kun Hou ◽  
Jinlu Yu
Keyword(s):  
Blood Flow ◽  
Arteriovenous Malformation ◽  
Endovascular Treatment ◽  
Vertebral Artery ◽  
Arteriovenous Fistula ◽  
Vascular Diseases ◽  
Posterior Circulation ◽  
Anterior Spinal Artery ◽  
Collateral Channel

The cervical anterior spinal artery (ASA) is a very important artery arising from the intracranial vertebral artery (VA). It can play different roles in endovascular treatment (EVT) of spinal vascular diseases. The current understanding of these roles is incomplete; therefore, we performed this review. We found that cervical ASA can be involved in many spinal vascular diseases, such as arteriovenous fistula (AVF), arteriovenous malformation (AVM), and aneurysm, and can serve as a collateral channel in proximal VA occlusion. In AVF and AVM, when the cervical ASA is involved, it often plays the role of an accomplice or victim because it acts as the feeder or as a bystander that does not provide blood flow to the AVF and AVM. In cervical ASA aneurysm, the ASA is a victim. During EVT of VA aneurysms or stenoses, the cervical ASA ostia can be covered or occluded, resulting in ASA ischemia. In this situation, the ASA is a victim. In VA occlusion or the subclavian steal phenomenon, the cervical ASA can serve as a collateral channel to provide blood flow to the posterior circulation. In this case, the ASA plays the role of a friend. According to the role of the cervical ASA in spinal vascular diseases, EVT should be determined “case by case.” Most importantly, when EVT is performed to treat these diseases, the cervical ASA axis must be preserved. Therefore, understanding the role of the cervical ASA in spinal vascular diseases is crucial.

Effect of decreased O2 supply on skeletal muscle oxygenation and O2 consumption during sepsis: role of heterogeneous capillary spacing and blood flow

2006 ◽  
Vol 290 (6) ◽  
pp. H2277-H2285 ◽  
Author(s):  
Daniel Goldman ◽  
Ryon M. Bateman ◽  
Christopher G. Ellis
Keyword(s):  
Blood Flow ◽  
Three Dimensional ◽  
Capillary Density ◽  
Diffusion Limitation ◽  
Capillary Networks ◽  
Skeletal Muscle Oxygenation ◽  
O2 Supply ◽  
Increased Blood Flow ◽  
Blood Flow Heterogeneity

One of the main aspects of the initial phase of the septic inflammatory response to a bacterial infection is abnormal microvascular perfusion, including decreased functional capillary density (FCD) and increased blood flow heterogeneity. On the other hand, one of the most important phenomena observed in the later stages of sepsis is an increased dependence of tissue O2 utilization on the convective O2 supply. This “pathological supply dependency” is associated with organ failure and poor clinical outcomes. Here, a detailed theoretical model of capillary-to-tissue O2 transport during sepsis is used to examine the origins of abnormal supply dependency. With use of three-dimensional arrays of capillaries with heterogeneous spacing and blood flow, steady-state O2 transport is simulated numerically during reductions in the O2 supply. Increased supply dependency is shown to occur in sepsis for hypoxic (decreased hemoglobin O2 saturation) and stagnant (decreased blood flow) hypoxia. For stagnant hypoxia, a reduction in FCD with decreasing blood flow is necessary to obtain the observed increase in supply dependency. Our results imply that supply dependency observed under normal conditions does not have its origin at the level of individual capillaries. In sepsis, however, diffusion limitation and shunting of O2 by individual capillaries occur to a degree that is dependent on the heterogeneity of septic injury and the arrangement of capillary networks. Thus heterogeneous stoppage of individual capillaries is a likely factor in pathological supply dependency.

Capillary Growth: Role of Mechanical Factors

Physiology ◽  
1988 ◽  
Vol 3 (3) ◽  
pp. 117-120
Author(s):  
O Hudlicka
Keyword(s):  
Blood Flow ◽  
Blood Cells ◽  
Skeletal Muscles ◽  
Physiological Conditions ◽  
Capillary Growth ◽  
Vessel Growth ◽  
Mechanical Factors ◽  
Increased Blood Flow ◽  
Stimulation Of

Although various growth factors initiate angiogenesis under pathological circumstances, vessel growth in physiological conditions (e.g., development, training) is related to increased blood flow. This article stresses the role of blood flow in the stimulation of capillary growth in skeletal muscles and in the heart. Also discussed are various components (blood pressure, wall tension, shear stress, blood cells-endothelium interaction) possibly involved in angiogenesis.

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