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.

Immunology of the vessel wall

2017 ◽  
Author(s):  
Göran K. Hansson
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Vascular Disease ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Vascular Wall ◽  
Point Of View ◽  
Health And Disease ◽  
Inflammatory Vascular Disease

This chapter provides an overview of the vascular wall and its cells from an immunological point of view, discusses the capacity of vascular cells to promote and regulate immune responses, and outlines interactions between the vasculature and the immune system in health and disease. The role of immune mechanisms in vascular diseases is discussed, with a focus on atherosclerosis, a chronic inflammatory vascular disease.

Mechanical factors and the regulation of perfusion through atelectatic lung in pigs

1982 ◽  
Vol 52 (3) ◽  
pp. 647-654 ◽  
Author(s):  
S. Enjeti ◽  
P. B. Terry ◽  
H. A. Menkes ◽  
R. J. Traystman
Keyword(s):  
Blood Flow ◽  
Vascular Conductance ◽  
Hemodynamic Responses ◽  
Closed Chest ◽  
Open Chest ◽  
Regional Hemodynamics ◽  
Mechanical Factors

The role of mechanical interdependence in the perfusion of atelectatic lung was studied in two ways: a) regional hemodynamics were compared before (control) and after the development of lobar and sublobar atelectasis, and b) the effect of thoracotomy on regional hemodynamics was assessed. With lobar atelectasis mean lobar blood flow and vascular conductance decreased to 60% of control. Sublobar atelectasis caused mean sublobar blood flow and vascular conductance to decrease to 6% of control. Opening the chest after production of lobar atelectasis caused blood flow to fall to 50% of control. When sublobar atelectasis was produced in the open chest, sublobar blood flow decreased to 25% of control measurements made prior to thoracotomy. We conclude that with a closed chest, sublobar vascular distortion mediated by mechanical interdependence may be an important mechanism responsible for the differences in hemodynamic responses to atelectasis between lobes and sublobar regions.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period

2012 ◽  
Vol 167 (2) ◽  
pp. 145-156 ◽  
Author(s):  
Theodora Pappa ◽  
Maria Alevizaki
Keyword(s):  
Vascular Disease ◽  
Postmenopausal Women ◽  
Sex Steroids ◽  
Carotid Artery Disease ◽  
Subclinical Atherosclerosis ◽  
Vascular Diseases ◽  
Future Research ◽  
Postmenopausal Period ◽  
Endogenous Estrogen

ObjectiveCardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period.Design and methodsWe performed a PubMed search using the terms ‘endogenous estrogen’, ‘androgen’, ‘cardiovascular disease’, ‘cerebro-vascular disease’, ‘stroke’, ‘carotid artery disease’, and ‘subclinical atherosclerosis’.ResultsThe majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive.ConclusionsMost studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

Abstract 8: Endothelial TFEB Regulates Postischemic Angiogenesis via AMPKalpha Activation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Yanbo Fan ◽  
Haocheng Lu ◽  
Wenying Liang ◽  
Yanhong Guo ◽  
Ji Zhang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Kinase ◽  
Transgenic Mice ◽  
Vascular Disease ◽  
Molecular Mechanisms ◽  
Blood Perfusion ◽  
Aortic Ring ◽  
Tube Formation ◽  
Genetically Engineered

Rationale: Postischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of angiogenesis are not fully unraveled. Transcription factor-EB (TFEB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in the vascular disease is less understood. Objective: We aim to determine the role of endothelial TFEB in postischemic angiogenesis and underlying molecular mechanism. Methods and Results: In a murine hindlimb ischemic model, we demonstrated that TFEB was upregulated in the ischemic skeletal muscle tissue. Utilizing genetically-engineered endothelial cell (EC) specific TFEB transgenic mice, we investigated the function of TFEB in postischemic angiogenesis. We observed improved blood perfusion and increased capillary density in the EC-specific TFEB transgenic mice compared with the wild-type littermates (n = 8-9 for each group, p < 0.01). Furthermore, we found that blood flow recovery was attenuated in EC-selective TFEB deficient mice compared with control mice (n =8-9 for each group, p< 0.01). In aortic ring cultures, we found that TFEB transgene significantly increased the vessel sprouting. Adenovirus-mediated TFEB overexpression promoted EC tube formation whereas small interfering RNA (siRNA)-mediated TFEB knockdown suppressed tube formation in ECs. Mechanistically, TFEB activated calcium/calmodulin-dependent protein kinase kinase-β and AMP-activated protein kinase (AMPK)-α signaling pathway. Through pharmacological inactivation and siRNA-mediated knockdown of AMPKα, we demonstrated that AMPKα is necessary for TFEB to regulate tube formation in ECs. Conclusions: In summary, our data demonstrate that TFEB is a positive regulator of angiogenesis through activation of AMPKα signaling, suggesting that TFEB constitutes a novel molecular target for ischemic vascular disease.

Role of the bronchial circulation in ischemia-reperfusion lung injury

1994 ◽  
Vol 76 (1) ◽  
pp. 259-265 ◽  
Author(s):  
D. B. Pearse ◽  
E. M. Wagner
Keyword(s):  
Blood Flow ◽  
Ischemia Reperfusion ◽  
Vasa Vasorum ◽  
Lung Water ◽  
Edema Formation ◽  
Pulmonary Vascular Permeability ◽  
Pulmonary Vessel ◽  
Pulmonary Arterial ◽  
Vessel Integrity

Bronchial arterial (BA) perfusion could modify pulmonary arterial (PA) ischemia-reperfusion (IR) injury by promoting clearance of peribronchial edema or limiting edema formation through maintenance of pulmonary vessel integrity via bronchopulmonary anastomotic or pulmonary vasa vasorum flow. The purpose of this study was to determine the effect of BA perfusion on IR injury in isolated sheep lungs. In 12 lungs (BA++) the BA was perfused throughout 30 min of PA ischemia and 180 min of reperfusion. In 12 lungs (BA-+) BA perfusion was begun with PA reperfusion, and in 15 lungs (BA--) the BA was never perfused. After 180 min, extravascular lung water was less (P < 0.05) in BA++ and B-+ lungs [4.70 +/- 0.16 and 4.57 +/- 0.18 g/g blood-free dry lung (bfdl)] than in BA-- lungs (5.23 +/- 0.19 g/g bfdl). The reflection coefficient for albumin was greater (P < 0.05) in BA++ and BA-+ (0.57 +/- 0.06 and 0.75 +/- 0.03) than in BA-- lungs (0.44 +/- 0.04). The filtration coefficient in BA++ and BA-+ lungs (0.016 +/- 0.006 and 0.015 +/- 0.006 g.min-1 x mmHg-1 x kg-1) was not different from that in BA-- lungs (0.025 +/- 0.006 g.min-1 x mmHg-1 x kg-1). These results suggest that BA perfusion decreased reperfusion edema by attenuating the increase in pulmonary vascular permeability caused by IR injury. Moreover the result in BA-+ lungs suggests that the protective effect was mediated by BA perfusion of PA vasa vasorum rather than bronchopulmonary anastomotic flow, which was trivial compared with PA blood flow.

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.

Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall

2020 ◽  
Author(s):  
Yanan Guo ◽  
Binjie Yan ◽  
Yu Gui ◽  
Zhihan Tang ◽  
Shi Tai ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Vascular Wall ◽  
Potential Impact

The Art and Science of Visualizing Simulated Blood-Flow Dynamics

Leonardo ◽  
2007 ◽  
Vol 40 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Dolores A. Hangan Steinman ◽  
David A. Steinman
Keyword(s):  
Blood Flow ◽  
Vascular Disease ◽  
Human Body ◽  
Flow Dynamics ◽  
Art And Science ◽  
Blood Flow Dynamics

The increasing use of computer enhancement and simulation to reveal the unseen human body brings with it challenges, opportunities and responsibilities at the interface of art and science. Here they are presented and discussed in the context of efforts to understand the role of blood-flow dynamics in vascular disease.

scholarly journals Central Role of Metabolism in Endothelial Cell Function and Vascular Disease

Physiology ◽  
2017 ◽  
Vol 32 (2) ◽  
pp. 126-140 ◽  
Author(s):  
Laura Bierhansl ◽  
Lena-Christin Conradi ◽  
Lucas Treps ◽  
Mieke Dewerchin ◽  
Peter Carmeliet
Keyword(s):  
Endothelial Cell ◽  
Vascular Disease ◽  
Cell Function ◽  
Current Knowledge ◽  
Vascular Diseases ◽  
Vascular Endothelial ◽  
Endothelial Cell Function ◽  
Vascular Beds

The importance of endothelial cell (EC) metabolism and its regulatory role in the angiogenic behavior of ECs during vessel formation and in the function of different EC subtypes determined by different vascular beds has been recognized only in the last few years. Even more importantly, apart from a role of nitric oxide and reactive oxygen species in EC dysfunction, deregulations of EC metabolism in disease only recently received increasing attention. Although comprehensive metabolic characterization of ECs still needs further investigation, the concept of targeting EC metabolism to treat vascular disease is emerging. In this overview, we summarize EC-specific metabolic pathways, describe the current knowledge on their deregulation in vascular diseases, and give an outlook on how vascular endothelial metabolism can serve as a target to normalize deregulated endothelium.

Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required

2010 ◽  
Vol 42A (1) ◽  
pp. 8-23 ◽  
Author(s):  
Renate Kopp ◽  
Thorsten Schwerte ◽  
Margit Egg ◽  
Adolf Michael Sandbichler ◽  
Bernhard Egger ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Oxygen Transport ◽  
Hypoxia Inducible Factor ◽  
Bulk Diffusion ◽  
Control Fish ◽  
Hypoxic Conditions ◽  
Atrial Contraction ◽  
Oxygen Carrying Capacity ◽  
Molecular Signals

In the present study, the zebrafish breakdance mutant ( bre) was used to assess the role of blood flow in development because it has been previously shown that bre larvae have a chronically reduced cardiac output as a result of ventricular contraction following only every second atrial contraction in addition to an atrial bradycardia. We confirmed a 50% reduction compared with control fish and further showed that blood flow in the caudal part of the dorsal aorta decreased by 80%. Associated with these reductions in blood flow were indications of developmental retardation in bre mutants, specifically delayed hatching, reduced cell proliferation, and a transiently decreased growth rate. Surprisingly, an increased red blood cell concentration and an earlier appearance of trunk vessels in bre larvae indicated some compensation to convective oxygen transport, although in previous studies it has been shown that zebrafish larvae at this stage obtain oxygen by bulk diffusion. In bre animals immunohistochemical analyses showed a significant increase in hypoxia inducible factor 1 (HIF)-α protein expression, comparable with wild-type larvae that were raised under hypoxic conditions. Accordingly, the expression of some hif downstream genes was affected. Furthermore, Affymetrix microarray analyses revealed a large number of genes that were differently expressed comparing control and bre larvae, and the number even increased with proceeding development. The results showed that a chronic reduction in blood flow generated hypoxic molecular signals despite partial compensation by increased oxygen carrying capacity and transiently slowed the overall development of zebrafish bre larvae.

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