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  1. Article: Involvement of overweight and lipid metabolism in the development of pulmonary hypertension under conditions of chronic intermittent hypoxia.

    Siques, Patricia / Brito, Julio / Ordenes, Stefany / Pena, Eduardo

    Pulmonary circulation

    2020  Volume 10, Issue 1 Suppl, Page(s) 42–49

    Abstract: There is growing evidence that exposure to hypoxia, regardless of the source, elicits several metabolic responses in individuals. These responses are constitutive and are usually observed under hypoxia but vary according to the type of exposure. The aim ... ...

    Abstract There is growing evidence that exposure to hypoxia, regardless of the source, elicits several metabolic responses in individuals. These responses are constitutive and are usually observed under hypoxia but vary according to the type of exposure. The aim of this review was to describe the involvement of obesity and lipid metabolism in the development of high-altitude pulmonary hypertension and in the development of acute mountain sickness under chronic intermittent hypoxia. Overweight or obesity, which are common in individuals with long-term chronic intermittent hypoxia exposure (high-altitude miners, shift workers, and soldiers), are thought to play a major role in the development of acute mountain sickness and high-altitude pulmonary hypertension. This association may be rooted in the interactions between obesity-related metabolic and physical alterations, such as increased waist circumference and neck circumference, among others, which lead to critical ventilation impairments; these impairments aggravate hypoxemia at high altitude, thereby triggering high-altitude diseases. Overweight and obesity are strongly associated with higher mean pulmonary artery pressure in the context of long-term chronic intermittent hypoxia. Remarkably, de novo synthesis of triglycerides by the sterol regulatory element-binding protein-1c pathway has been demonstrated, mainly due to the upregulation of stearoyl-CoA desaturase-1, which is also associated with the same outcomes. Therefore, overweight, obesity, and other metabolic conditions may hinder proper acclimatization. The involved mechanisms include respiratory impairment, alteration of the nitric oxide pathways, inflammatory status, reactive oxygen species imbalance, and other metabolic changes; however, further studies are required.
    Language English
    Publishing date 2020-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2638089-4
    ISSN 2045-8940 ; 2045-8932
    ISSN (online) 2045-8940
    ISSN 2045-8932
    DOI 10.1177/2045894020930626
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of Zinc on the Right Cardiovascular Circuit in Long-Term Hypobaric Hypoxia in Wistar Rats.

    Arriaza, Karem / Brito, Julio / Siques, Patricia / Flores, Karen / Ordenes, Stefany / Aguayo, Daniel / López, María Del Rosario / Arribas, Silvia M

    International journal of molecular sciences

    2023  Volume 24, Issue 11

    Abstract: Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation ... ...

    Abstract Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation in prolonged hypobaric hypoxia on HIF2α/MTF-1/MT/ZIP12/PKCε pathway in the lung and RVH. Wistar rats were exposed to hypobaric hypoxia for 30 days and randomly allocated into three groups: chronic hypoxia (CH); intermittent hypoxia (2 days hypoxia/2 days normoxia; CIH); and normoxia (sea level control; NX). Each group was subdivided (n = 8) to receive either 1% Zn sulfate solution (z) or saline (s) intraperitoneally. Body weight, hemoglobin, and RVH were measured. Zn levels were evaluated in plasma and lung tissue. Additionally, the lipid peroxidation levels, HIF2α/MTF-1/MT/ZIP12/PKCε protein expression and pulmonary artery remodeling were measured in the lung. The CIH and CH groups showed decreased plasma Zn and body weight and increased hemoglobin, RVH, and vascular remodeling; the CH group also showed increased lipid peroxidation. Zn administration under hypobaric hypoxia upregulated the HIF2α/MTF-1/MT/ZIP12/PKCε pathway and increased RVH in the intermittent zinc group. Under intermittent hypobaric hypoxia, Zn dysregulation could participate in RVH development through alterations in the pulmonary HIF2α/MTF1/MT/ZIP12/PKCε pathway.
    MeSH term(s) Rats ; Animals ; Rats, Wistar ; Zinc ; Lung/metabolism ; Hypoxia/metabolism ; Hypertrophy, Right Ventricular/etiology ; Body Weight
    Chemical Substances Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2023-05-31
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24119567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Long-Term Pannexin 1 Ablation Produces Structural and Functional Modifications in Hippocampal Neurons.

    Flores-Muñoz, Carolina / García-Rojas, Francisca / Pérez, Miguel A / Santander, Odra / Mery, Elena / Ordenes, Stefany / Illanes-González, Javiera / López-Espíndola, Daniela / González-Jamett, Arlek M / Fuenzalida, Marco / Martínez, Agustín D / Ardiles, Álvaro O

    Cells

    2022  Volume 11, Issue 22

    Abstract: Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies such as epilepsy and Alzheimer's disease (AD). The Panx1 channel ablation alters the hippocampus's glutamatergic neurotransmission, synaptic plasticity, ...

    Abstract Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies such as epilepsy and Alzheimer's disease (AD). The Panx1 channel ablation alters the hippocampus's glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, Panx1-knockout (Panx1-KO) mice still retain the ability to learn, suggesting that compensatory mechanisms stabilize their neuronal activity. Here, we show that the absence of Panx1 in the adult brain promotes a series of structural and functional modifications in the Panx1-KO hippocampal synapses, preserving spontaneous activity. Compared to the wild-type (WT) condition, the adult hippocampal neurons of Panx1-KO mice exhibit enhanced excitability, a more complex dendritic branching, enhanced spine maturation, and an increased proportion of multiple synaptic contacts. These modifications seem to rely on the actin-cytoskeleton dynamics as an increase in the actin polymerization and an imbalance between the Rac1 and the RhoA GTPase activities were observed in Panx1-KO brain tissues. Our findings highlight a novel interaction between Panx1 channels, actin, and Rho GTPases, which appear to be relevant for synapse stability.
    MeSH term(s) Animals ; Mice ; Connexins/metabolism ; Actins ; Nerve Tissue Proteins/metabolism ; Hippocampus/metabolism ; Neurons/metabolism
    Chemical Substances Connexins ; Actins ; Nerve Tissue Proteins ; Panx1 protein, mouse
    Language English
    Publishing date 2022-11-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11223646
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation.

    Flores, Karen / Siques, Patricia / Brito, Julio / Ordenes, Stefany / Arriaza, Karem / Pena, E / León-Velarde, Fabiola / López, Rosario / López de Pablo, Ángel L / Arribas, Silvia

    Frontiers in physiology

    2020  Volume 11, Page(s) 342

    Abstract: Background: Both chronic hypoxia (CH) and long-term chronic intermittent hypoxia (CIH) exposure lead to right ventricular hypertrophy (RVH). Weight loss is an effective intervention to improve cardiac function and energy metabolism in cardiac ... ...

    Abstract Background: Both chronic hypoxia (CH) and long-term chronic intermittent hypoxia (CIH) exposure lead to right ventricular hypertrophy (RVH). Weight loss is an effective intervention to improve cardiac function and energy metabolism in cardiac hypertrophy. Likewise, caloric restriction (CR) also plays an important role in this cardioprotection through AMPK activation. We aimed to determine the influence of body weight (BW) on RVH, AMPK and related variables by comparing rats exposed to both hypoxic conditions.
    Methods: Sixty male adult rats were separated into two groups (
    Results: A lower degree of RVH, higher AMPK activation, and no activation of mTOR were found in the CR groups exposed to hypobaric hypoxia compared to the AL groups (
    Conclusion: Maintaining a low weight before and during exposure to high-altitude hypoxia, during either CH or CIH, could prevent a major degree of RVH. This cardioprotection would likely be due to the activation of AMPK. Thus, body weight is a factor that might contribute to RVH at high altitudes.
    Language English
    Publishing date 2020-04-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2020.00342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Long-Term Chronic Intermittent Hypobaric Hypoxia Induces Glucose Transporter (GLUT4) Translocation Through AMP-Activated Protein Kinase (AMPK) in the Soleus Muscle in Lean Rats.

    Siques, Patricia / Brito, Julio / Flores, Karen / Ordenes, Stefany / Arriaza, Karem / Pena, Eduardo / León-Velarde, Fabiola / López de Pablo, Ángel L / Gonzalez, M C / Arribas, Silvia

    Frontiers in physiology

    2018  Volume 9, Page(s) 799

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2018-06-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2018.00799
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Adventitial alterations are the main features in pulmonary artery remodeling due to long-term chronic intermittent hypobaric hypoxia in rats.

    Brito, Julio / Siques, Patricia / Arribas, Silvia M / López de Pablo, Angel L / González, M Carmen / Naveas, Nelson / Arriaza, Karem / Flores, Karen / León-Velarde, Fabiola / Pulido, Ruth / Ordenes, Stefany / López, M Rosario

    BioMed research international

    2015  Volume 2015, Page(s) 169841

    Abstract: Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other ... ...

    Abstract Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer.
    MeSH term(s) Adventitia/pathology ; Adventitia/physiopathology ; Altitude Sickness/pathology ; Altitude Sickness/physiopathology ; Animals ; Disease Models, Animal ; Hypoxia/pathology ; Hypoxia/physiopathology ; Pulmonary Artery/pathology ; Pulmonary Artery/physiopathology ; Rats ; Rats, Wistar ; Vascular Remodeling
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2698540-8
    ISSN 2314-6141 ; 2314-6133
    ISSN (online) 2314-6141
    ISSN 2314-6133
    DOI 10.1155/2015/169841
    Database MEDical Literature Analysis and Retrieval System OnLINE

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