Placental mitochondrial function as a driver of angiogenesis and placental dysfunction

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yolanda Correia ◽  
Julia Scheel ◽  
Shailendra Gupta ◽  
Keqing Wang
Keyword(s):  
Mitochondrial Function ◽  
Environmental Changes ◽  
Angiogenic Factors ◽  
The Body ◽  
Angiogenic Factor ◽  
Foetal Development ◽  
Hormone Synthesis ◽  
Placental Dysfunction ◽  
Healthy Pregnancy ◽  
Mitochondrial Adaptations

Abstract The placenta is a highly vascularized and complex foetal organ that performs various tasks, crucial to a healthy pregnancy. Its dysfunction leads to complications such as stillbirth, preeclampsia, and intrauterine growth restriction. The specific cause of placental dysfunction remains unknown. Recently, the role of mitochondrial function and mitochondrial adaptations in the context of angiogenesis and placental dysfunction is getting more attention. The required energy for placental remodelling, nutrient transport, hormone synthesis, and the reactive oxygen species leads to oxidative stress, stemming from mitochondria. Mitochondria adapt to environmental changes and have been shown to adjust their oxygen and nutrient use to best support placental angiogenesis and foetal development. Angiogenesis is the process by which blood vessels form and is essential for the delivery of nutrients to the body. This process is regulated by different factors, pro-angiogenic factors and anti-angiogenic factors, such as sFlt-1. Increased circulating sFlt-1 levels have been linked to different preeclamptic phenotypes. One of many effects of increased sFlt-1 levels, is the dysregulation of mitochondrial function. This review covers mitochondrial adaptations during placentation, the importance of the anti-angiogenic factor sFlt-1in placental dysfunction and its role in the dysregulation of mitochondrial function.

scholarly journals Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction

2006 ◽  
Vol 203 (9) ◽  
pp. 2165-2175 ◽  
Author(s):  
Guillermina Girardi ◽  
Dmitry Yarilin ◽  
Joshua M. Thurman ◽  
V. Michael Holers ◽  
Jane E. Salmon
Keyword(s):  
Complement Activation ◽  
Angiogenic Factors ◽  
Growth Restriction ◽  
Angiogenic Factor ◽  
Vegf Receptor ◽  
Placental Development ◽  
Triggered Release ◽  
Placental Dysfunction

Immune mechanisms have been implicated in placental dysfunction in patients with recurrent miscarriages and intrauterine growth restriction (IUGR), but the mediators are undefined. Here we show that complement activation, particularly C5a, is a required intermediary event in the pathogenesis of placental and fetal injury in an antibody-independent mouse model of spontaneous miscarriage and IUGR, and that complement activation causes dysregulation of the angiogenic factors required for normal placental development. Pregnancies complicated by miscarriage or growth restriction were characterized by inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor 1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation in vivo blocked the increase in sVEGFR-1 and rescued pregnancies. In vitro stimulation of monocytes with products of the complement cascade directly triggered release of sVEGFR-1, which sequesters VEGF. These studies provide the first evidence linking the complement system to angiogenic factor imbalance associated with placental dysfunction, and identify a new effector of immune-triggered pregnancy complications.

scholarly journals Wearable Vibration Sensor for Measuring the Wing Flapping of Insects

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 593
Author(s):  
Ryota Yanagisawa ◽  
Shunsuke Shigaki ◽  
Kotaro Yasui ◽  
Dai Owaki ◽  
Yasuhiro Sugimoto ◽  
...  
Keyword(s):  
High Speed ◽  
Environmental Changes ◽  
Underlying Mechanism ◽  
Indirect Measurement ◽  
Feedback Mechanism ◽  
The Body ◽  
Vibration Sensor ◽  
Wingbeat Frequency ◽  
Film Sensor ◽  
Insect Wing

In this study, we fabricated a novel wearable vibration sensor for insects and measured their wing flapping. An analysis of insect wing deformation in relation to changes in the environment plays an important role in understanding the underlying mechanism enabling insects to dynamically interact with their surrounding environment. It is common to use a high-speed camera to measure the wing flapping; however, it is difficult to analyze the feedback mechanism caused by the environmental changes caused by the flapping because this method applies an indirect measurement. Therefore, we propose the fabrication of a novel film sensor that is capable of measuring the changes in the wingbeat frequency of an insect. This novel sensor is composed of flat silver particles admixed with a silicone polymer, which changes the value of the resistor when a bending deformation occurs. As a result of attaching this sensor to the wings of a moth and a dragonfly and measuring the flapping of the wings, we were able to measure the frequency of the flapping with high accuracy. In addition, as a result of simultaneously measuring the relationship between the behavior of a moth during its search for an odor source and its wing flapping, it became clear that the frequency of the flapping changed depending on the frequency of the odor reception. From this result, a wearable film sensor for an insect that can measure the displacement of the body during a particular behavior was fabricated.

scholarly journals Individuals Diagnosed with Binge-Eating Disorder Have DNA Hypomethylated Sites in Genes of the Metabolic System: A Pilot Study

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1413
Author(s):  
Mariana Lizbeth Rodríguez-López ◽  
José Jaime Martínez-Magaña ◽  
David Ruiz-Ramos ◽  
Ana Rosa García ◽  
Laura Gonzalez ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Eating Disorder ◽  
Protein Kinase ◽  
Binge Eating ◽  
Binge Eating Disorder ◽  
Environmental Changes ◽  
Diagnostic Category ◽  
The Body ◽  
Metabolic System ◽  
Genome Wide

Binge-eating disorder, recently accepted as a diagnostic category, is differentiated from bulimia nervosa in that the former shows the presence of binge-eating episodes and the absence of compensatory behavior. Epigenetics is a conjunct of mechanisms (like DNA methylation) that regulate gene expression, which are dependent on environmental changes. Analysis of DNA methylation in eating disorders shows that it is reduced. The present study aimed to analyze the genome-wide DNA methylation differences between individuals diagnosed with BED and BN. A total of 46 individuals were analyzed using the Infinium Methylation EPIC array. We found 11 differentially methylated sites between BED- and BN-diagnosed individuals, with genome-wide significance. Most of the associations were found in genes related to metabolic processes (ST3GAL4, PRKAG2, and FRK), which are hypomethylated genes in BED. Cg04781532, located in the body of the PRKAG2 gene (protein kinase AMP-activated non-catalytic subunit gamma 2), was hypomethylated in individuals with BED. Agonists of PRKAG2, which is the subunit of AMPK (AMP-activated protein kinase), are proposed to treat obesity, BED, and BN. The present study contributes important insights into the effect that BED could have on PRKAG2 activation.

scholarly journals VEGF Regulation of Angiogenic Factors via Inflammatory Signaling in Myeloproliferative Neoplasms

2021 ◽  
Vol 22 (13) ◽  
pp. 6671
Author(s):  
Tijana Subotički ◽  
Olivera Mitrović Ajtić ◽  
Emilija Živković ◽  
Miloš Diklić ◽  
Dragoslava Đikić ◽  
...  
Keyword(s):  
Protein Expression ◽  
Chronic Inflammation ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Angiogenic Factors ◽  
Mtor Signaling ◽  
Angiogenic Factor ◽  
Inflammatory Signaling ◽  
Gene And Protein Expression ◽  
Hel Cells

Background: Chronic inflammation has been recognized in neoplastic disorders, including myeloproliferative neoplasm (MPN), as an important regulator of angiogenesis. Aims: We investigated the influence of vascular endothelial growth factor (VEGF) and pro-inflammatory interleukin-6 (IL-6) on the expression of angiogenic factors, as well as inflammation-related signaling in mononuclear cells (MNC) of patients with MPN and JAK2V617F positive human erythroleukemic (HEL) cells. Results: We found that IL-6 did not change the expression of angiogenic factors in the MNC of patients with MPN and HEL cells. However, IL-6 and the JAK1/2 inhibitor Ruxolitinib significantly increased angiogenic factors—endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor-1 alpha (HIF-1α)—in patients with polycythemia vera (PV). Furthermore, VEGF significantly increased the expression of HIF-1α and eNOS genes, the latter inversely regulated by PI3K and mTOR signaling in the MNC of primary myelofibrosis (PMF). VEGF and inhibitors of inflammatory JAK1/2, PI3K, and mTOR signaling reduced the eNOS protein expression in HEL cells. VEGF also decreased the expression of eNOS and HIF-1α proteins in the MNC of PMF. In contrast, VEGF increased eNOS and HIF-1α protein expression in the MNC of patients with PV, which was mediated by the inflammatory signaling. VEGF increased the level of IL-6 immunopositive MNC of MPN. In summary, VEGF conversely regulated gene and protein expression of angiogenic factors in the MNC of PMF, while VEGF increased angiogenic factor expression in PV mediated by the inflammation-related signaling. Conclusion: The angiogenic VEGF induction of IL-6 supports chronic inflammation that, through positive feedback, further promotes angiogenesis with concomitant JAK1/2 inhibition.

Exercise and Mitochondrial Function: Importance and InferenceA Mini Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Vaishali K. ◽  
Nitesh Kumar ◽  
Vanishree Rao ◽  
Rakesh Krishna Kovela ◽  
Mukesh Kumar Sinha
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Skeletal Muscles ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Present Review ◽  
Age Related ◽  
Exercise Induced ◽  
Mitochondrial Adaptations

: Skeletal muscles must generate and distribute energy properly in order to function perfectly. Mitochondria in skeletal muscle cells form vast networks to meet this need, and their functions may improve as a result of exercise. In the present review, we discussed exercise-induced mitochondrial adaptations, age-related mitochondrial decline, and a biomarker as a mitochondrial function indicator and exercise interference.

scholarly journals Diesel Exhaust Particle Exposure Compromises Alveolar Macrophage Mitochondrial Bioenergetics

2019 ◽  
Vol 20 (22) ◽  
pp. 5598
Author(s):  
Jonathan L. Gibbs ◽  
Blake W. Dallon ◽  
Joshua B. Lewis ◽  
Chase M. Walton ◽  
Juan A. Arroyo ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Diesel Exhaust ◽  
Critical Role ◽  
Cell Communication ◽  
Diesel Exhaust Particle ◽  
Diesel Exhaust Particles ◽  
The Body ◽  
Whole Body ◽  
H2o2 Production ◽  
Pulmonary Macrophages

Diesel exhaust particles (DEPs) are known pathogenic pollutants that constitute a significant quantity of air pollution. Given the ubiquitous presence of macrophages throughout the body, including the lungs, as well as their critical role in tissue and organismal metabolic function, we sought to determine the effect of DEP exposure on macrophage mitochondrial function. Following daily DEP exposure in mice, pulmonary macrophages were isolated for mitochondrial analyses, revealing reduced respiration rates and dramatically elevated H2O2 levels. Serum ceramides and inflammatory cytokines were increased. To determine the degree to which the changes in mitochondrial function in macrophages were not dependent on any cross-cell communication, primary pulmonary murine macrophages were used to replicate the DEP exposure in a cell culture model. We observed similar changes as seen in pulmonary macrophages, namely diminished mitochondrial respiration, but increased H2O2 production. Interestingly, when treated with myriocin to inhibit ceramide biosynthesis, these DEP-induced mitochondrial changes were mitigated. Altogether, these data suggest that DEP exposure may compromise macrophage mitochondrial and whole-body function via pathologic alterations in macrophage ceramide metabolism.

scholarly journals A Mathematical Model of anIn VitroExperiment to Investigate Endothelial Cell Migration

2002 ◽  
Vol 4 (4) ◽  
pp. 251-270 ◽  
Author(s):  
M. J. Plank ◽  
B. D. Sleeman ◽  
P. F. Jones
Keyword(s):  
Mathematical Model ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Three Dimensional ◽  
Cell Movement ◽  
Quantitative Model ◽  
Angiogenic Factors ◽  
Endothelial Cell Migration ◽  
Angiogenic Factor

Angiogenesis, the growth of new blood vessels from existing ones, is an important, yet not fully understood, process and is involved in diseases such as rheumatoid arthritis, diabetic retinopathy and solid tumour growth. Central to the process of angiogenesis are endothelial cells (EC), which line all blood vessels, and are capable of forming new capillaries by migration, proliferation and lumen formation. We construct a cell-based mathematical model of an experiment (Vernon, R.B. and Sage, E.H. (1999) “A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices”,Microvasc. Res.57, 118–133) carried out to assess the response of EC to various diffusible angiogenic factors, which is a crucial part of angiogenesis. The model for cell movement is based on the theory of reinforced random walks and includes both chemotaxis and chemokinesis. Three-dimensional simulations are run and the results correlate well with the experimental data. The experiment cannot easily distinguish between chemotactic and chemokinetic effects of the angiogenic factors. We, therefore, also run two-dimensional simulations of a hypothetical experiment, with a point source of angiogenic factor. This enables directed (gradient-driven) EC migration to be investigated independently of undirected (diffusion-driven) migration.

scholarly journals Aetiological factors in left-handedness

2005 ◽  
Vol 133 (11-12) ◽  
pp. 532-534 ◽  
Author(s):  
Sanja Milenkovic ◽  
Goran Belojevic ◽  
Radojka Kocijancic
Keyword(s):  
Genetic Factors ◽  
The Body ◽  
Intrauterine Environment ◽  
Foetal Development ◽  
Ultrasound Exposure ◽  
The Past ◽  
Left Handedness ◽  
Left Handed ◽  
Efferent Pathways ◽  
Genetically Determined

Lateralisation associates the extremities and senses of one side of the body, which are connected by afferent and efferent pathways, with the primary motor and sensory areas of the hemisphere on the opposite side. Dominant laterality denotes the appearance of a dominant extremity or sense in the performance of complex psychomotor activities. Laterality is manifested both as right-handedness or left-handedness, which are functionally equivalent and symmetrical in the performance of activities. Right-handedness is significantly more common than left-handedness. Genetic theory is most widely accepted in explaining the onset of lateralisation. According to this theory, the models of brain organisation asymmetry (anatomical, functional, and biochemical) are strongly, genetically determined. However, the inability to clearly demonstrate the association between genetic factors and left-handedness has led researchers to investigate the effects of the environment on left-handedness. Of particular interest are the intrauterine environment and the factors influencing foetal development, of which hormones and ultrasound exposure are the most significant. It has been estimated that an extra five cases of nonright-handed lateralisation can be expected in every 100 males who were exposed to ultrasound in utero compared to those who were not. Socio-cultural pressure on left-handed individuals was much more severe in the past, which is confirmed by scientific findings that left-handedness is present in 13% of individuals in their twenties, while in less than 1% of individuals in their eighties.

Patients with Pain During Pregnancy

2016 ◽  
Author(s):  
Charles J. Fox ◽  
Alan D. Kaye ◽  
Elyse Cornett ◽  
Katherine Stammen ◽  
Michael Franklin
Keyword(s):  
Abdominal Pain ◽  
Back Pain ◽  
Pregnant Women ◽  
Pelvic Pain ◽  
Joint Laxity ◽  
The Body ◽  
Healthy Pregnancy ◽  
Pain Analgesics ◽  
Chronic Severe Pain ◽  
Anxiety Depression

Most women experience some degree of pain during pregnancy. Back pain occurs in about half of all pregnant women, with pain typically in the low back due to the physiologic changes in the body that occur with pregnancy, such as weight gain, changed center of gravity, increased ligament and joint laxity, and altered posture. Pelvic pain, leg cramps, and abdominal pain are all common among pregnant women. Many women who have pain during pregnancy are reluctant to use analgesics due to concerns about what the medications may do to their unborn child. Because of this, it is hypothesized that many women are either undertreated for pain or do not receive any treatment. Chronic, severe pain that is ineffectively treated is associated with hypertension, anxiety, and depression, all of which do not lead to a healthy pregnancy. A variety of interventional procedures are commonly performed during pregnancy that can safely alleviate pain. This review goes into detail about the types of pain treatments that are available to pregnant women and are safe and effective in alleviating pregnancy-related pain. Keywords: Pelvic pain, leg cramps, abdominal pain, hypertension, anxiety, depression, joint laxity, ligament laxity, back pain, analgesics, pregnancy

Somatostatin and Octreotide: Literature Review and Description of Therapeutic Activity in Pancreatic Neoplasia

1988 ◽  
Vol 22 (2) ◽  
pp. 99-106 ◽  
Author(s):  
Stephen M. Longnecker
Keyword(s):  
The Body ◽  
Endocrine Tumors ◽  
Hormone Synthesis ◽  
System A ◽  
Inappropriate Secretion ◽  
Hormonal Imbalance ◽  
Long Acting ◽  
Therapeutic Activities ◽  
Pancreatic Neoplasia ◽  
Endogenous Substances

The somatostatins represent endogenous substances that serve a diversity of functions in the body. These activities are just beginning to be understood and could have major implications in the treatment of human disease. Their chief pharmacologic activities lie in the modification or modulation of protein hormone synthesis of the gastrointestinal system; a great many other systems may be involved as well. Since the discovery of the therapeutic potentials of naturally isolated somatostatins, attempts have been made to design newer analogs more conducive to practical use. Such an example is long-acting somatostatin analog octreotide. Literature has recently begun to appear describing the therapeutic activities of this and other similar compounds and the first steps to understanding their clinical pharmacology are being taken. Surprising activity has been found in the palliative treatment of a wide variety of formerly resistant gastrointestinal syndromes and endocrine tumors. These activities may have considerable future impact on the treatment of disease involving hormonal imbalance or inappropriate secretion.

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