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Anatomical Record (Hoboken, N.J. : 2007) Jun 2008Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial... (Review)
Review
Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial up-regulation of von Willebrand factor and ICAM-1 with reduced expression of caveolin-1. These changes have been termed age-related pseudocapillarization. The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age-related changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age-related diseases.
Topics: Aging; Animals; Corrosion Casting; Endocytosis; Endothelial Cells; Humans; Kupffer Cells; Liver; Liver Circulation; Microcirculation; Microscopy, Electron
PubMed: 18484614
DOI: 10.1002/ar.20661 -
American Journal of Physiology. Heart... May 2022Coronary microvascular disease (CMD), which affects the arterioles and capillary endothelium that regulate myocardial perfusion, is an increasingly recognized source of... (Review)
Review
Coronary microvascular disease (CMD), which affects the arterioles and capillary endothelium that regulate myocardial perfusion, is an increasingly recognized source of morbidity and mortality, particularly in the setting of metabolic syndrome. The coronary endothelium plays a pivotal role in maintaining homeostasis, though factors such as diabetes, hypertension, hyperlipidemia, and obesity can contribute to endothelial injury and consequently arteriolar vasomotor dysfunction. These disturbances in the coronary microvasculature clinically manifest as diminished coronary flow reserve, which is a known independent risk factor for cardiac death, even in the absence of macrovascular atherosclerotic disease. Therefore, a growing body of literature has examined the molecular mechanisms by which coronary microvascular injury occurs at the level of the endothelium and the consequences on arteriolar vasomotor responses. This review will begin with an overview of normal coronary microvascular physiology, modalities of measuring coronary microvascular function, and clinical implications of CMD. These introductory topics will be followed by a discussion of recent advances in the understanding of the mechanisms by which inflammation, oxidative stress, insulin resistance, hyperlipidemia, hypertension, shear stress, endothelial cell senescence, and tissue ischemia dysregulate coronary endothelial homeostasis and arteriolar vasomotor function.
Topics: Coronary Circulation; Coronary Vessels; Endothelium, Vascular; Humans; Hypertension; Microcirculation; Microvessels
PubMed: 35333122
DOI: 10.1152/ajpheart.00603.2021 -
Cells Aug 2021The microcirculation includes an invisible network of micro-vessels that are up to a few hundred microns in diameter [...].
The microcirculation includes an invisible network of micro-vessels that are up to a few hundred microns in diameter [...].
Topics: Animals; Cell- and Tissue-Based Therapy; Endothelium, Vascular; Humans; Microcirculation; Stem Cells
PubMed: 34440914
DOI: 10.3390/cells10082144 -
Microcirculation (New York, N.Y. : 1994) Nov 2008Theoretical modeling approaches have made important contributions to research in the biological sciences, including the microcirculation, and their value is increasingly... (Review)
Review
Theoretical modeling approaches have made important contributions to research in the biological sciences, including the microcirculation, and their value is increasingly recognized. However, misconceptions about the nature and role of theoretical models persist, and such work is often presented in a way that does not maximize its value, especially for scientists who are not themselves using such models. In this review, a categorization of models as phenomenological, qualitative conceptual, quantitative conceptual, or predictive is proposed, and the characteristics of each type are discussed. Recommendations are made for the presentation of models and for the future development of modeling approaches. The concepts discussed are generally applicable to the theoretical modeling of biological systems and are illustrated by using examples of modeling in microcirculation research.
Topics: Animals; Biological Transport; Classification; Computational Biology; Humans; Interdisciplinary Communication; Microcirculation; Models, Cardiovascular; Research; Research Design; Rheology
PubMed: 18946803
DOI: 10.1080/10739680802349734 -
Critical Care (London, England) Mar 2018This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at... (Review)
Review
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .
Topics: Administration, Intravenous; Decision Support Techniques; Fluid Therapy; Humans; Intensive Care Units; Microcirculation
PubMed: 29558989
DOI: 10.1186/s13054-018-1993-1 -
Circulation Journal : Official Journal... Aug 2009
Topics: Animals; Atherosclerosis; Endothelium, Vascular; Humans; Microcirculation; Oxidants; Oxidative Stress; Postprandial Period; Vitamins
PubMed: 19628923
DOI: 10.1253/circj.cj-09-0445 -
Journal of Molecular and Cellular... Apr 2012Atherosclerosis of conduit epicardial arteries is the principal culprit behind the complications of coronary heart disease, but a growing body of literature indicates... (Review)
Review
Atherosclerosis of conduit epicardial arteries is the principal culprit behind the complications of coronary heart disease, but a growing body of literature indicates that the coronary microcirculation also contributes substantially to the pathophysiology of cardiovascular disease. An understanding of mechanisms regulating microvascular function in humans is an essential foundation for understanding the role in disease, especially since these regulatory mechanisms vary substantially across species and vascular beds. In fact all subjects whose coronary tissue was used in the studies described have medical conditions that warrant cardiac surgery, thus relevance to the normal human must be inferential and is based on tissue from subjects without known arteriosclerotic disease. This review will focus on recent advances in the physiological and pathological mechanisms of coronary microcirculatory control, describing a robust plasticity in maintaining endothelial control over dilation, including mechanisms that are most relevant to the human heart. This article is part of a Special Issue entitled "Coronary Blood Flow".
Topics: Coronary Circulation; Endothelium, Vascular; Humans; Microcirculation; Vasodilation
PubMed: 22033434
DOI: 10.1016/j.yjmcc.2011.10.003 -
Microcirculation (New York, N.Y. : 1994) 2005Vascular smooth muscle (VSM) cells, endothelial cells (EC), and pericytes that form the walls of vessels in the microcirculation express a diverse array of ion channels... (Review)
Review
Vascular smooth muscle (VSM) cells, endothelial cells (EC), and pericytes that form the walls of vessels in the microcirculation express a diverse array of ion channels that play an important role in the function of these cells and the microcirculation in both health and disease. This brief review focuses on the K+ channels expressed in smooth muscle and endothelial cells in arterioles. Microvascular VSM cells express at least four different classes of K+ channels, including inward-rectifier K+ channels (Kin), ATP-sensitive K+ channels (KATP), voltage-gated K+ channels (Kv), and large conductance Ca2+-activated K+ channels (BKCa). VSM KIR participate in dilation induced by elevated extracellular K+ and may also be activated by C-type natriuretic peptide, a putative endothelium-derived hyperpolarizing factor (EDHF). Vasodilators acting through cAMP or cGMP signaling pathways in VSM may open KATP, Kv, and BKCa, causing membrane hyperpolarization and vasodilation. VSMBKc. may also be activated by epoxides of arachidonic acid (EETs) identified as EDHF in some systems. Conversely, vasoconstrictors may close KATP, Kv, and BKCa through protein kinase C, Rho-kinase, or c-Src pathways and contribute to VSM depolarization and vasoconstriction. At the same time Kv and BKCa act in a negative feedback manner to limit depolarization and prevent vasospasm. Microvascular EC express at least 5 classes of K+ channels, including small (sKCa) and intermediate(IKCa) conductance Ca2+-activated K+ channels, Kin, KATP, and Kv. Both sK and IK are opened by endothelium-dependent vasodilators that increase EC intracellular Ca2+ to cause membrane hyper-polarization that may be conducted through myoendothelial gap junctions to hyperpolarize and relax arteriolar VSM. KIR may serve to amplify sKCa- and IKCa-induced hyperpolarization and allow active transmission of hyperpolarization along EC through gap junctions. EC KIR channels may also be opened by elevated extracellular K+ and participate in K+-induced vasodilation. EC KATP channels may be activated by vasodilators as in VSM. Kv channels may provide a negative feedback mechanism to limit depolarization in some endothelial cells.
Topics: Animals; Endothelium, Vascular; Humans; Microcirculation; Muscle, Smooth, Vascular; Potassium Channels
PubMed: 15804979
DOI: 10.1080/10739680590896072 -
Critical Care (London, England) Jul 2019The endothelial glycocalyx (eGC) covers the luminal surface of the vascular endothelium and plays an important protective role in systemic inflammatory states and... (Observational Study)
Observational Study
BACKGROUND
The endothelial glycocalyx (eGC) covers the luminal surface of the vascular endothelium and plays an important protective role in systemic inflammatory states and particularly in sepsis. Its breakdown leads to capillary leak and organ dysfunction. Moreover, sepsis-induced alterations of sublingual microcirculation are associated with a worse clinical outcome. The present study was performed to investigate the associations between eGC dimensions and established parameters of microcirculation dysfunction in sepsis.
METHODS
This observational, prospective, cross-sectional study included 40 participants, of which 30 critically ill septic patients were recruited from intensive care units of a university hospital and 10 healthy volunteers served as controls. The established microcirculation parameters were obtained sublingually and analyzed according to the current recommendations. In addition, the perfused boundary region (PBR), an inverse parameter of the eGC dimensions, was measured sublingually, using novel data acquisition and analysis software (GlycoCheck™). Moreover, we exposed living endothelial cells to 5% serum from a subgroup of study participants, and the delta eGC breakdown, measured with atomic force microscopy (AFM), was correlated with the paired PBR values.
RESULTS
In septic patients, sublingual microcirculation was impaired, as indicated by a reduced microvascular flow index (MFI) and a reduced proportion of perfused vessels (PPV) compared to those in healthy controls (MFI, 2.93 vs 2.74, p = 0.002; PPV, 98.53 vs 92.58, p = 0.0004). PBR values were significantly higher in septic patients compared to those in healthy controls, indicating damage of the eGC (2.04 vs 2.34, p < 0.0001). The in vitro AFM data correlated exceptionally well with paired PBR values obtained at the bedside (rs = - 0.94, p = 0.02). Both PBR values and microcirculation parameters correlated well with the markers of critical illness. Interestingly, no association was observed between the PBR values and established microcirculation parameters.
CONCLUSION
Our findings suggest that eGC damage can occur independently of microcirculatory impairment as measured by classical consensus parameters. Further studies in critically ill patients are needed to unravel the relationship of glycocalyx damage and microvascular impairment, as well as their prognostic and therapeutic importance in sepsis.
TRIAL REGISTRATION
Retrospectively registered: Clinicaltrials.gov, NCT03960307.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Endothelial Cells; Female; Glycocalyx; Humans; Male; Microcirculation; Middle Aged; Prospective Studies; Resuscitation; Retrospective Studies; Sepsis
PubMed: 31340868
DOI: 10.1186/s13054-019-2542-2 -
Reviews in Endocrine & Metabolic... Mar 2013In most humans, obesity is associated with a chronic low-grade inflammatory reaction occurring in several organ tissues, including the adipose tissue. Infiltration of... (Review)
Review
In most humans, obesity is associated with a chronic low-grade inflammatory reaction occurring in several organ tissues, including the adipose tissue. Infiltration of bone marrow derived leukocytes (granulocytes, monocytes, lymphocytes) into expanding adipose depots appears to be an integral component of inflammation in obesity. Circulating leukocytes invade organ tissues mainly through post-capillary venules in the microcirculation. The endothelium of the post-capillary venules acts as a gatekeeper to leukocyte adhesion and extravasation by displacing on its luminal surface adhesion molecules that bind the adhesive receptors expressed on circulating leukocytes. Several studies investigating the impact of obesity on the microcirculation have demonstrated the occurrence of microvascular dysfunction in experimental animal model of obesity, as well as in obese humans. To date though, working hypotheses and study designs have favored the view that microvascular alterations are secondary to adipose tissue dysfunction. Indeed, a significant amount of data exists in the scientific literature to support the concept that microvascular dysfunction may precede and cause adipose tissue inflammation in obesity. Through review of key published data, this article prospectively presents the concept that in response to nutrients overload the vascular endothelium of the microcirculation acutely activates inflammatory pathways that initiate infiltration of leukocytes in visceral adipose tissue, well before weight gain and overt obesity. The anatomical and physiological heterogeneity of different microcirculations is also discussed toward the understanding of how obesity induces different inflammatory phenotypes in visceral and subcutaneous fat depots.
Topics: Adipose Tissue; Animals; Humans; Inflammation; Microcirculation; Selectins
PubMed: 23378133
DOI: 10.1007/s11154-013-9236-x