981 DIET-INDUCED ENDOTHELIAL STIFFNESS, CELLULAR HYPOXIA, AND ABNORMAL ANGIOGENIC SIGNALING IN PREECLAMPSIA

2012 ◽  
Vol 30 ◽  
pp. e283-e284
Author(s):  
Nancy Hart
Keyword(s):  
Cellular Hypoxia ◽  
Endothelial Stiffness

scholarly journals Senescence Increases Choroidal Endothelial Stiffness and Susceptibility to Complement Injury: Implications for Choriocapillaris Loss in AMD

2016 ◽  
Vol 57 (14) ◽  
pp. 5910 ◽  
Author(s):  
Andrea P. Cabrera ◽  
Arun Bhaskaran ◽  
Jun Xu ◽  
Xiao Yang ◽  
Harry A. Scott ◽  
...  
Keyword(s):  
Endothelial Stiffness

THE INFLUENCE OF CLINICAL AND LABORATORY FACTORS ON THE DEVELOPMENT OF HEMODYNAMIC COMPLICATIONS DURING ANESTHESIA IN CARDIAC SURGERY

2021 ◽  
Vol 19 (4) ◽  
pp. 367-375
Author(s):  
R. E. Yakubtsevich ◽  
◽  
K. O. Kratkou ◽  
Keyword(s):  
Cardiac Surgery ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Postoperative Period ◽  
Modern Medicine ◽  
New Methods ◽  
Laboratory Markers ◽  
Tnf Α ◽  
Cellular Hypoxia ◽  
Methods Of Treatment

Background. Currently, cardioanesthesiology is one of the most actively developing areas of modern medicine. Thanks to new methods of treatment, the contingent of patients for whom it became possible to undergo cardiac surgery has significantly expanded. The main problems that lead to hemodynamic complications are endothelial dysfunction and cellular hypoxia. Purpose. To present data on the influence of clinical and laboratory factors of endothelial dysfunction and cellular hypoxia on the development of hemodynamic complications during anesthesia in cardiac surgery. Material and methods. The review and analysis of literature data from 49 sources is presented. Results. The laboratory markers of endothelial dysfunction leading to the development of major hemodynamic complications in cardiovascular diseases are MPC-1, CRP, NO, TNF-α, IL-6, homocysteine. Conclusion. The data obtained indicate a significant effect of cell markers (MPC-1, CRP, NO, TNF-A, IL-6, homocysteine) as well as clinical and laboratory factors of endothelial dysfunction not only on the development of major diseases of the cardiovascular system, but also on their complications. An early study of these markers can improve anesthesia during cardiac surgery as well as reduce complications in the postoperative period.

Abstract P295: Endothelial Sodium Channel Activation Promotes Cardiac Stiffness in Obese Female Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Javad Habibi ◽  
Annayya R Aroor ◽  
Lixin Ma ◽  
Guanghong Jia ◽  
Adam Whaley-Connell ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Low Dose ◽  
Interstitial Fibrosis ◽  
Diastolic Heart Failure ◽  
The United States ◽  
High Fat ◽  
Female Mice ◽  
Obese Female ◽  
High Fructose ◽  
Endothelial Stiffness

Cardiac diastolic dysfunction (DD) and diastolic heart failure is increasing in concert with obesity and aging population in the United States. In obese and diabetic women, DD is more common than in their male counterparts. This disproportionate increase in DD in obese females may partly explain their loss of sex-related cardiovascular (CV) disease protection. Recent studies have suggested a role for endothelial sodium channel (ENaC) activation in promotion of endothelial stiffness and suppression of flow- (nitric oxide) mediated vasodilation. Moreover, increased mineralocorticoid receptor (MR) activation mediated endothelial stiffness is promoted, in part, by ENaC activation. In this regard, we have recently reported increased plasma aldosterone levels, aortic and cardiac stiffness, and cardiac and vascular MR expression in female mice fed a high fat and high fructose diet (western diet [WD]). This increase in CV stiffness was prevented by very low dose MR antagonism. Accordingly, we hypothesized that inhibition of MR-mediated ENaC activation by using a very low dose of the ENaC inhibitor, amiloride would prevent cardiac stiffening (DD) in WD-fed female mice. Four week old C57BL6/J mice were fed a WD containing high fat (46%), sucrose (17.5%), and high fructose corn syrup (17.5%) with or without a very low dose of amiloride (1mg/kg/day) for 16 weeks. Amiloride significantly attenuated WD-induced impairment of cardiac relaxation in vivo as measured by high resolution magnetic resonance imaging (MRI) as well as cardiac interstitial fibrosis as measured by immunohistochemistry by picrosirius red staining. Moreover, amiloride prevented the development of DD in obese female mice without having effects on blood pressure. These observations support a role for ENaC activation in diet-induced cardiac stiffening (DD) in obese females.

Cellular energy utilization and supply during hypoxia in embryonic cardiac myocytes

1996 ◽  
Vol 270 (1) ◽  
pp. L44-L53 ◽  
Author(s):  
G. R. Budinger ◽  
N. Chandel ◽  
Z. H. Shao ◽  
C. Q. Li ◽  
A. Melmed ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Myocytes ◽  
Energy Demand ◽  
Adenine Nucleotide ◽  
Energy Utilization ◽  
Embryonic Chick ◽  
O2 Uptake ◽  
Progressive Hypoxia ◽  
Cellular Hypoxia

Studies of intact hearts suggest that cardiac myocytes may have the ability to reversibly suppress metabolic activity and energy demand in states of regional hypoperfusion. However, an ability to suppress respiration in response to hypoxia has never been demonstrated in isolated myocytes. To test this, isolated embryonic chick cardiac myocytes were exposed to progressive hypoxia while their rate of O2 uptake and concentrations of lactate, ATP, ADP, AMP, and phosphocreatine were measured. Compared with the value obtained at an oxygen tension (PO2) of 120 Torr, cellular O2 uptake decreased by 28 +/- 14% (SD) at PO2 = 50 Torr and by 64 +/- 25% at PO2 = 20 Torr (P < 0.05). This decrease was similar after 1 min or 2 h of hypoxia, was sustained for 16 h, and was completely reversible within 2 min after reoxygenation. The reduction in O2 uptake was associated with a decrease in the rate of ATP turnover, but no change in adenine nucleotide or phosphocreatine concentrations. In myocytes adherent to glass cover-slips, O2 uptake and contractile motion were decreased after 30-60 min at 50 and 20 Torr, compared with normoxic values. O2 uptake also was significantly decreased at 50 and 20 Torr in myocytes incubated with N,N,N',N'-tetramethyl-p-phenylenediamine, which suggests that the catalytic activity of cytochrome-c oxidase was partially inhibited during hypoxia. In summary, these results demonstrate that embryonic chick cardiac myocytes can suppress their rates of ATP demand, ATP utilization, and O2 uptake during moderate hypoxia through a mechanism that involves a reversible inhibition of cytochrome-c oxidase. This mechanism may represent a protective response to cellular hypoxia.

Noninvasive Cellular Oxygenation Measurement During Graded Hypoxia Using Visible–Near-Infrared Spectroscopy

2020 ◽  
Vol 74 (10) ◽  
pp. 1263-1273
Author(s):  
Lorilee S.L. Arakaki ◽  
Wayne A. Ciesielski ◽  
D. Michael McMullan ◽  
Kenneth A. Schenkman
Keyword(s):  
Near Infrared ◽  
Cerebral Oxygenation ◽  
Serum Lactate ◽  
Arterial Blood ◽  
Direct Knowledge ◽  
Steady State Serum ◽  
Cellular Hypoxia ◽  
Low Levels ◽  
Changes Over Time ◽  
Inspired Oxygen

In critically ill patients, direct knowledge of intracellular pO2 would allow for identification of cellular hypoxia, which when prolonged leads to organ failure. We have developed a visible–near-infrared optical system that noninvasively measures myoglobin saturation, which is directly related to intracellular pO2, from the surface of the skin. We used an animal model of graded hypoxia from low levels of inspired oxygen ( n = 5) and verified that low intracellular pO2 is correlated with high steady-state serum lactate values. In addition, the pO2 gradient between arterial blood and inside muscle cells was 83 mm Hg at 21% O2, but fell to 24 mm Hg at 8% O2. Continuous myoglobin saturation measurement in skeletal muscle displayed the same trends as cerebral oxygenation with no lag in changes over time, demonstrating its relevance as a measure of systemic oxygenation.

Brief hypoxic stress suppresses postbacteremic NF-κB activation and TNF-α bioactivity in perfused liver

2000 ◽  
Vol 279 (1) ◽  
pp. R99-R108 ◽  
Author(s):  
Laura L. Loftis ◽  
Cheryl A. Johanns ◽  
Andrew J. Lechner ◽  
George M. Matuschak
Keyword(s):  
Gene Expression ◽  
Nuclear Translocation ◽  
Nuclear Factor Κb ◽  
Mobility Shift ◽  
Gram Negative ◽  
Nuclear Extracts ◽  
Tnf Α ◽  
Cellular Hypoxia ◽  
Electrophoretic Mobility Shift Assays ◽  
Rat Livers

Reductions in hepatic O2 delivery are common early after gram-negative bacteremic sepsis owing to cardiopulmonary dysfunction and derangements in sinusoidal perfusion. Although gram-negative endotoxin and cellular hypoxia independently enhance activation of nuclear factor-κB (NF-κB) via generation of reactive O2 species (ROS), the combination of these stimuli downregulates hepatic TNF-α gene expression. Here we tested the hypothesis that hypoxic suppression of postbacteremic TNF-α gene expression is transcriptionally mediated by reduced activation of NF-κB. Buffer-perfused rat livers ( n = 52) were studied over 180 min after intraportal infection at t = 0 with 109 live Escherichia coli (EC), serotype O55:B5, or 0.9% NaCl controls under normoxic conditions, compared with 0.5 h of constant-flow hypoxia (Po 2 ∼41 ± 7 Torr) beginning at t = 30 min, followed by 120 min of reoxygenation. In parallel studies, tissue was obtained at peak hypoxia ( t = 60 min). To determine the role of xanthine oxidase (XO)-induced ROS in modulating NF-κB activity after hypoxia/reoxygenation (H/R), livers were pretreated with the XO inhibitor allopurinol, with results confirmed in organs of tungstate-fed animals. Electrophoretic mobility shift assays were performed on nuclear extracts of whole liver lysates using32P-labeled oligonucleotides specific for NF-κB. Compared with normoxic EC controls, hypoxia reduced postbacteremic NF-κB nuclear translocation and TNF-α bioactivity, independent of reoxygenation, tissue levels of reduced glutathione, or posthypoxic O2 consumption. XO inhibition reversed the hypoxic suppression of NF-κB nuclear translocation and ameliorated decreases in cell-associated TNF-α. Thus decreases in hepatic O2delivery reduce postbacteremic nuclear translocation of NF-κB and hepatic TNF-α biosynthesis by signaling mechanisms involving low-level generation of XO-mediated ROS.

Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis

JAMA ◽  
1992 ◽  
Vol 267 (11) ◽  
pp. 1503-1510 ◽  
Author(s):  
R. S. Hotchkiss
Keyword(s):  
Cellular Hypoxia

scholarly journals Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy

2020 ◽  
Vol 12 (536) ◽  
pp. eaay0271 ◽  
Author(s):  
Angela Lek ◽  
Yuanfan Zhang ◽  
Keryn G. Woodman ◽  
Shushu Huang ◽  
Alec M. DeSimone ◽  
...  
Keyword(s):  
Cell Death ◽  
Muscular Dystrophy ◽  
Phenotypic Selection ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Loss Of Function ◽  
Hypoxia Response ◽  
Genome Wide ◽  
A Genome ◽  
Structural And Functional Properties ◽  
Cellular Hypoxia

The emergence of CRISPR-Cas9 gene-editing technologies and genome-wide CRISPR-Cas9 libraries enables efficient unbiased genetic screening that can accelerate the process of therapeutic discovery for genetic disorders. Here, we demonstrate the utility of a genome-wide CRISPR-Cas9 loss-of-function library to identify therapeutic targets for facioscapulohumeral muscular dystrophy (FSHD), a genetically complex type of muscular dystrophy for which there is currently no treatment. In FSHD, both genetic and epigenetic changes lead to misexpression of DUX4, the FSHD causal gene that encodes the highly cytotoxic DUX4 protein. We performed a genome-wide CRISPR-Cas9 screen to identify genes whose loss-of-function conferred survival when DUX4 was expressed in muscle cells. Genes emerging from our screen illuminated a pathogenic link to the cellular hypoxia response, which was revealed to be the main driver of DUX4-induced cell death. Application of hypoxia signaling inhibitors resulted in increased DUX4 protein turnover and subsequent reduction of the cellular hypoxia response and cell death. In addition, these compounds proved successful in reducing FSHD disease biomarkers in patient myogenic lines, as well as improving structural and functional properties in two zebrafish models of FSHD. Our genome-wide perturbation of pathways affecting DUX4 expression has provided insight into key drivers of DUX4-induced pathogenesis and has identified existing compounds with potential therapeutic benefit for FSHD. Our experimental approach presents an accelerated paradigm toward mechanistic understanding and therapeutic discovery of a complex genetic disease, which may be translatable to other diseases with well-established phenotypic selection assays.

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