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Journal of Cerebral Blood Flow and... Feb 2016Pericytes, spatially isolated contractile cells on capillaries, have been reported to control cerebral blood flow physiologically, and to limit blood flow after... (Review)
Review
Pericytes, spatially isolated contractile cells on capillaries, have been reported to control cerebral blood flow physiologically, and to limit blood flow after ischaemia by constricting capillaries and then dying. Paradoxically, a recent paper dismisses the idea of pericytes controlling cerebral blood flow, despite confirming earlier data showing a role for pericytes. We show that these discrepancies are apparent rather than real, and depend on the new paper defining pericytes differently from previous reports. An objective definition of different sub-classes of pericyte along the capillary bed is needed to develop novel therapeutic approaches for stroke and disorders caused by pericyte malfunction.
Topics: Animals; Capillaries; Cerebrovascular Circulation; Humans; Pericytes; Terminology as Topic
PubMed: 26661200
DOI: 10.1177/0271678X15610340 -
Nature Oct 2020In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to...
In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood. Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex 'Swiss-cheese'-like morphologies and distinct functions. The first cell type, which we term the 'aerocyte', is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap ('general' capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air-blood barrier and gas exchange in health, disease and evolution.
Topics: Aging; Alligators and Crocodiles; Animals; Biological Evolution; Capillaries; Cell Division; Cell Self Renewal; Cellular Senescence; Humans; Male; Mice; Pulmonary Alveoli; Pulmonary Gas Exchange; Stem Cells; Turtles
PubMed: 33057196
DOI: 10.1038/s41586-020-2822-7 -
The Journal of Clinical Investigation Apr 2024Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the... (Review)
Review
Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the forehead have an increased risk of developing a neurocutaneous disorder called encephalotrigeminal angiomatosis or Sturge-Weber syndrome (SWS), with complications including seizure, developmental delay, glaucoma, and vision loss. In 2013, a groundbreaking study revealed causative activating somatic mutations in the gene (GNAQ) encoding guanine nucleotide-binding protein Q subunit α (Gαq) in CM and SWS patient tissues. In this Review, we discuss the disease phenotype, the causative GNAQ mutations, and their cellular origin. We also present the endothelial Gαq-related signaling pathways, the current animal models to study CM and its complications, and future options for therapeutic treatment. Further work remains to fully elucidate the cellular and molecular mechanisms underlying the formation and maintenance of the abnormal vessels.
Topics: Infant, Newborn; Animals; Humans; Glaucoma; Models, Animal; Mutation; Capillaries; Vascular Malformations
PubMed: 38618955
DOI: 10.1172/JCI172842 -
Comparative Biochemistry and... Mar 2021The capillary bed constitutes the obligatory pathway for almost all oxygen (O) and substrate molecules as they pass from blood to individual cells. As the largest organ,... (Review)
Review
The capillary bed constitutes the obligatory pathway for almost all oxygen (O) and substrate molecules as they pass from blood to individual cells. As the largest organ, by mass, skeletal muscle contains a prodigious surface area of capillaries that have a critical role in metabolic homeostasis and must support energetic requirements that increase as much as 100-fold from rest to maximal exercise. In 1919 Krogh's 3 papers, published in the Journal of Physiology, brilliantly conflated measurements of muscle capillary function at rest and during contractions with Agner K. Erlang's mathematical model of O diffusion. These papers single-handedly changed the perception of capillaries from passive vessels serving at the mercy of their upstream arterioles into actively contracting vessels that were recruited during exercise to elevate blood-myocyte O flux. Although seminal features of Krogh's model have not withstood the test of time and subsequent technological developments, Krogh is credited with helping found the field of muscle microcirculation and appreciating the role of the capillary bed and muscle O diffusing capacity in facilitating blood-myocyte O flux. Today, thanks in large part to Krogh, it is recognized that comprehending the role of the microcirculation, as it supports perfusive and diffusive O conductances, is fundamental to understanding skeletal muscle plasticity with exercise training and resolving the mechanistic bases by which major pathologies including heart failure and diabetes cripple exercise tolerance and cerebrovascular dysfunction predicates impaired executive function.
Topics: Animals; Capillaries; Diffusion; Humans; Muscle Cells; Muscles; Oxygen
PubMed: 33242636
DOI: 10.1016/j.cbpa.2020.110852 -
Minerva Anestesiologica May 2003Microcirculatory alterations have been widely described in experimental models of sepsis, however the microcirculation have long been neglected in septic patients as... (Review)
Review
Microcirculatory alterations have been widely described in experimental models of sepsis, however the microcirculation have long been neglected in septic patients as traditional techniques do not allow the visualisation of the microcirculation. The Orthogonal Polarization Spectral (OPS) imaging technique allows the direct visualisation of the microcirculation at the bedside. A selected review of the articles on the microcirculation in patients with sepsis using the OPS imaging technique, is made. Patients severe sepsis present a decrease in capillary density and a decrease in the proportion of the perfused capillaries. The severity of these alterations is more pronounced in non survivors than in survivors, and is related with the development of multiple organ failure. These alterations can be reversed by vasodilators, either topically applied or administered intravenously. Microvascular blood flow alterations are frequently observed in patients with sepsis and can have major pathophysiological implications.
Topics: Capillaries; Critical Illness; Diagnostic Imaging; Humans; Microcirculation; Point-of-Care Systems
PubMed: 12768172
DOI: No ID Found -
JCI Insight Jan 2022Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, glomerular filtration barrier...
Alport syndrome (AS) is a genetic disorder caused by mutations in type IV collagen that lead to defective glomerular basement membrane, glomerular filtration barrier (GFB) damage, and progressive chronic kidney disease. While the genetic basis of AS is well known, the molecular and cellular mechanistic details of disease pathogenesis have been elusive, hindering the development of mechanism-based therapies. Here, we performed intravital multiphoton imaging of the local kidney tissue microenvironment in a X-linked AS mouse model to directly visualize the major drivers of AS pathology. Severely distended glomerular capillaries and aneurysms were found accompanied by numerous microthrombi, increased glomerular endothelial surface layer (glycocalyx) and immune cell homing, GFB albumin leakage, glomerulosclerosis, and interstitial fibrosis by 5 months of age, with an intermediate phenotype at 2 months. Renal histology in mouse or patient tissues largely failed to detect capillary aberrations. Treatment of AS mice with hyaluronidase or the ACE inhibitor enalapril reduced the excess glomerular endothelial glycocalyx and blocked immune cell homing and GFB albumin leakage. This study identified central roles of glomerular mechanical forces and endothelial and immune cell activation early in AS, which could be therapeutically targeted to reduce mechanical strain and local tissue inflammation and improve kidney function.
Topics: Animals; Capillaries; Cellular Microenvironment; Disease Models, Animal; Humans; Intravital Microscopy; Kidney Glomerulus; Male; Mice; Nephritis, Hereditary
PubMed: 34793332
DOI: 10.1172/jci.insight.152676 -
American Journal of Ophthalmology May 2018To use the capillary-free zone along retinal arteries, a physiologic area of superficial avascularization, as an anatomic paradigm to investigate the reliability of... (Comparative Study)
Comparative Study
PURPOSE
To use the capillary-free zone along retinal arteries, a physiologic area of superficial avascularization, as an anatomic paradigm to investigate the reliability of optical coherence tomography angiography (OCTA) for visualizing the deep retinal circulation.
DESIGN
Validity analysis and laboratory investigation.
METHODS
Five normal human donor eyes (mean age 69.8 years) were perfusion-labeled with endothelial antibodies and the capillary networks of the perifovea were visualized using confocal scanning laser microscopy. Regions of the capillary-free zone along the retinal artery were imaged using OCTA in 16 normal subjects (age range 24-51 years). Then, 3 × 3-mm scans were acquired using the RTVue XR Avanti (ver. 2016.1.0.26; Optovue, Inc, Fremont, California, USA), PLEX Elite 9000 (ver. 1.5.0.15909; Zeiss Meditec, Inc, Dublin, California, USA), Heidelberg Spectralis OCT2 (Family acquisition module 6.7.21.0; Heidelberg Engineering, Heidelberg, Germany), and DRI-OCT Triton (Ver. 1.1.1; Topcon Corp, Tokyo, Japan). Images of the superficial plexus, deep vascular plexus, and a slab containing all vascular plexuses were generated using manufacturer-recommended default settings. Comparisons between histology and OCTA were performed.
RESULTS
Histologic analysis revealed that the capillary-free zone along the retinal artery was confined to the plane of the superficial capillary plexus and did not include the intermediate and deep capillary plexuses. Images derived from OCTA instruments demonstrated a prominent capillary-free zone along the retinal artery in slabs of the superficial plexus, deep plexus, and all capillary plexuses. The number of deep retinal capillaries seen in the capillary-free zone was significantly greater on histology than on OCTA (P < .001).
CONCLUSION
Using the capillary-free zone as an anatomic paradigm, we show that the deep vascular beds of the retina are not completely visualized using OCTA. This may be a limitation of current OCTA techniques.
Topics: Adult; Aged; Blood Circulation; Capillaries; Female; Fluorescein Angiography; Fovea Centralis; Healthy Volunteers; Histological Techniques; Humans; Male; Microscopy, Confocal; Middle Aged; Reproducibility of Results; Retinal Artery; Tissue Donors; Tomography, Optical Coherence; Young Adult
PubMed: 29470970
DOI: 10.1016/j.ajo.2018.02.007 -
Cells Dec 2019Atherosclerosis and associated ischemic organ dysfunction represent the number one cause of mortality worldwide. While the key drivers of atherosclerosis, arterial... (Review)
Review
Atherosclerosis and associated ischemic organ dysfunction represent the number one cause of mortality worldwide. While the key drivers of atherosclerosis, arterial hypertension, hypercholesterolemia and diabetes mellitus, are well known disease entities and their contribution to the formation of atherosclerotic plaques are intensively studied and well understood, less effort is put on the effect of these disease states on microvascular structure an integrity. In this review we summarize the pathological changes occurring in the vascular system in response to prolonged exposure to these major risk factors, with a particular focus on the differences between these pathological alterations of the vessel wall in larger arteries as compared to the microcirculation. Furthermore, we intend to highlight potential therapeutic strategies to improve microvascular function during atherosclerotic vessel disease.
Topics: Arteries; Atherosclerosis; Capillaries; Diabetes Mellitus; Endothelial Cells; Humans; Hypercholesterolemia; Hypertension; Microvessels; Plaque, Atherosclerotic
PubMed: 31878229
DOI: 10.3390/cells9010050 -
Journal of Muscle Research and Cell... Jun 2019It is widely acknowledged that maintenance of muscle, size, strength and endurance is necessary for quality of life and the role that skeletal muscle microcirculation... (Review)
Review
It is widely acknowledged that maintenance of muscle, size, strength and endurance is necessary for quality of life and the role that skeletal muscle microcirculation plays in muscle health is becoming increasingly clear. Here we discuss the role that skeletal muscle microcirculation plays in muscle function and plasticity. Besides the density of the capillary network, also the distribution of capillaries is crucial for adequate muscle oxygenation. While capillaries are important for oxygen delivery, the capillary supply to a fibre is related to fibre size rather than oxidative capacity. This link between fibre size and capillary supply is also reflected by the similar time course of hypertrophy and angiogenesis, and the cross-talk between capillaries and satellite cells. A dense vascular network may in fact be more important for a swift repair of muscle damage than the abundance of satellite cells and a lower capillary density may also attenuate the hypertrophic response. Capillary rarefaction does not only occur during ageing, but also during conditions as chronic heart failure, where endothelial apoptosis has been reported to precede muscle atrophy. It has been suggested that capillary rarefaction precedes sarcopenia. If so, stimulation of angiogenesis by for instance endurance training before a hypertrophic stimulus may enhance the hypertrophic response. The microcirculation may thus well be a little-explored target to improve muscle function and the success of rehabilitation programmes during ageing and chronic diseases.
Topics: Aging; Animals; Capillaries; Humans; Hypertrophy; Microcirculation; Muscle, Skeletal; Muscular Atrophy; Neovascularization, Physiologic; Satellite Cells, Skeletal Muscle
PubMed: 31165949
DOI: 10.1007/s10974-019-09520-2 -
Experimental Physiology Dec 2013The capillary bed constitutes a vast surface that facilitates exchange of O2, substrates and metabolites between blood and organs. In contracting skeletal muscle,... (Review)
Review
The capillary bed constitutes a vast surface that facilitates exchange of O2, substrates and metabolites between blood and organs. In contracting skeletal muscle, capillary blood flow and O2 diffusing capacity, as well as O2 flux, may increase two orders of magnitude above resting values. Chronic diseases, such as heart failure and diabetes, and also sepsis impair these processes, leading to compromised energetic, metabolic and, ultimately, contractile function. Among researchers seeking to understand blood-myocyte exchange in health and the basis for dysfunction in disease, there is a fundamental disconnect between microcirculation specialists and many physiologists and physiologist clinicians. While the former observe capillaries and capillary function directly (muscle intravital microscopy), the latter generally use indirect methodologies (e.g. post-mortem tissue analysis, 1-methyl xanthine, contrast-enhanced ultrasound, permeability-surface area product) and interpret their findings based upon August Krogh's observations made nearly a century ago. 'Kroghian' theory holds that only a small fraction of capillaries support red blood cell (RBC) flux in resting muscle, leaving the vast majority to be 'recruited' (i.e. to initiate RBC flux) during contractions, which would constitute the basis for increasing surface area for capillary exchange and reducing capillary-mitochondrial diffusion distances. Experimental techniques each have their strengths and weaknesses, and often the correct or complete answer to a problem emerges from integration across multiple technologies. Today, Krogh's entrenched 'capillary recruitment' hypothesis is challenged by direct observations of capillaries in contracting muscle, which is something that he and his colleagues could not do. Moreover, in the peer-reviewed scientific literature, application of a range of contemporary physiological technologies, including intravital microscopy of contracting muscle, magnetic resonance, near-infrared spectroscopy and phosphorescence quenching, combined with elegant in situ and in vivo models, suggest that the role of the capillary bed, at least in contracting muscle, is subserved without the necessity for de novo capillary recruitment of previously non-flowing capillaries. When viewed within the context of the capillary recruitment hypothesis, this evidence casts serious doubt on the interpretation of those data that are based upon Kroghian theory and indirect methodologies. Thus, today a wealth of evidence calls for a radical revision of blood-muscle exchange theory to one in which most capillaries support RBC flux at rest and, during contractions, capillary surface area is 'recruited' along the length of previously flowing capillaries. This occurs, in part, by elevating capillary haematocrit and extending the length of the capillary available for blood-myocyte exchange (i.e. longitudinal recruitment). Our understanding of blood-myocyte O2 and substrate/metabolite exchange in health and the mechanistic basis for dysfunction in disease demands no less.
Topics: Capillaries; Humans; Microcirculation; Muscle Cells; Muscle Contraction; Muscle, Skeletal; Oxygen; Regional Blood Flow; Rest; Ultrasonography
PubMed: 23995101
DOI: 10.1113/expphysiol.2013.073874