scholarly journals Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

2020 ◽  
Vol 11 ◽  
Author(s):  
Karen Flores ◽  
Patricia Siques ◽  
Julio Brito ◽  
Stefany Ordenes ◽  
Karem Arriaza ◽  
...  
Keyword(s):  
Body Weight ◽  
Right Ventricular ◽  
Hypobaric Hypoxia ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Lower Body ◽  
Ampk Activation ◽  
Hypoxia Exposure ◽  
Lower Body Weight

scholarly journals Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia

2020 ◽  
Vol 21 (17) ◽  
pp. 6421
Author(s):  
Eduardo Pena ◽  
Julio Brito ◽  
Samia El Alam ◽  
Patricia Siques
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Right Ventricular ◽  
Hypobaric Hypoxia ◽  
Ventricular Hypertrophy ◽  
Current Knowledge ◽  
Right Heart Failure ◽  
Right Ventricular Hypertrophy ◽  
Therapeutic Approaches ◽  
Inflammatory Molecules

High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent pulmonary arterial remodeling. These changes can lead to pulmonary hypertension and the development of right ventricular hypertrophy (RVH), right heart failure (RHF) and, ultimately to death. The aim of this review is to describe the most recent molecular pathways involved in the above conditions under this type of hypobaric hypoxia, including oxidative stress, inflammation, protein kinases activation and fibrosis, and the current therapeutic approaches for these conditions. This review also includes the current knowledge of long-term chronic intermittent hypobaric hypoxia. Furthermore, this review highlights the signaling pathways related to oxidative stress (Nox-derived O2.- and H2O2), protein kinase (ERK5, p38α and PKCα) activation, inflammatory molecules (IL-1β, IL-6, TNF-α and NF-kB) and hypoxia condition (HIF-1α). On the other hand, recent therapeutic approaches have focused on abolishing hypoxia-induced RVH and RHF via attenuation of oxidative stress and inflammatory (IL-1β, MCP-1, SDF-1 and CXCR-4) pathways through phytotherapy and pharmacological trials. Nevertheless, further studies are necessary.

Alpha-skeletal actin messenger RNA increases in acute right ventricular hypertrophy

1990 ◽  
Vol 258 (4) ◽  
pp. L173-L178 ◽  
Author(s):  
P. R. Bakerman ◽  
K. R. Stenmark ◽  
J. H. Fisher
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Hypobaric Hypoxia ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Hypoxic Exposure ◽  
Mrna Levels ◽  
Severe Pulmonary Hypertension ◽  
Cardiac Actin ◽  
Actin Mrna

Newborn calves exposed to hypobaric hypoxia develop severe pulmonary hypertension. Right ventricular hypertrophy and failure occur as a consequence of the increased pressure load. Alterations in right ventricular myocyte performance or differentiation could be reflected by the changes in the expression of contractile protein genes. We studied expression of contractile actin isotypes by measuring mRNA levels in total cellular RNA purified from right (RV) and left ventricles (LV) of calves with severe pulmonary hypertension after a 2-wk exposure to hypobaric hypoxia and age-matched controls. alpha-Skeletal actin mRNA was increased greater than 10-fold in the RV of hypertensive animals, whereas alpha-cardiac actin mRNA did not appear to change. alpha-Skeletal actin mRNA and alpha-cardiac actin mRNA did not increase in the LV of any of the hypoxic animals. After a 2-wk hypoxic exposure, calves were removed from the chamber. Two days later, RV alpha-skeletal actin mRNA decreased dramatically but was apparently elevated above that of an age-matched control. Thirty days after hypoxia, there appeared to be a persistent increase in RV alpha-skeletal actin mRNA. Although the physiological significance of these changes are unknown, an alteration in the RV myocyte phenotype has occurred.

scholarly journals Nox2 Upregulation and p38α MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia

2020 ◽  
Vol 21 (22) ◽  
pp. 8576
Author(s):  
Eduardo Pena ◽  
Patricia Siques ◽  
Julio Brito ◽  
Silvia M. Arribas ◽  
Rainer Böger ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Nadph Oxidase ◽  
Right Ventricular ◽  
Hypobaric Hypoxia ◽  
Ventricular Hypertrophy ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Right Ventricular Hypertrophy ◽  
Mapk Activation ◽  
Intermittent Hypobaric Hypoxia

One of the consequences of high altitude (hypobaric hypoxia) exposure is the development of right ventricular hypertrophy (RVH). One particular type of exposure is long-term chronic intermittent hypobaric hypoxia (CIH); the molecular alterations in RVH in this particular condition are less known. Studies show an important role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-induced oxidative stress and protein kinase activation in different models of cardiac hypertrophy. The aim was to determine the oxidative level, NADPH oxidase expression and MAPK activation in rats with RVH induced by CIH. Male Wistar rats were randomly subjected to CIH (2 days hypoxia/2 days normoxia; n = 10) and normoxia (NX; n = 10) for 30 days. Hypoxia was simulated with a hypobaric chamber. Measurements in the RV included the following: hypertrophy, Nox2, Nox4, p22phox, LOX-1 and HIF-1α expression, lipid peroxidation and H2O2 concentration, and p38α and Akt activation. All CIH rats developed RVH and showed an upregulation of LOX-1, Nox2 and p22phox and an increase in lipid peroxidation, HIF-1α stabilization and p38α activation. Rats with long-term CIH-induced RVH clearly showed Nox2, p22phox and LOX-1 upregulation and increased lipid peroxidation, HIF-1α stabilization and p38α activation. Therefore, these molecules may be considered new targets in CIH-induced RVH.

Angiotensin AT1receptor blockade fails to attenuate pressure-overload cardiac hypertrophy in fetal sheep

1997 ◽  
Vol 273 (4) ◽  
pp. R1501-R1508 ◽  
Author(s):  
Jeffrey L. Segar ◽  
Thomas D. Scholz ◽  
Kurt A. Bedell ◽  
Oliva M. Smith ◽  
David J. Huss ◽  
...  
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Left Ventricle ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Right Ventricular Hypertrophy ◽  
Fetal Sheep ◽  
Receptor Mrna

We examined the hypothesis that endogenous angiotensin II and angiotensin type 1 (AT1) receptors participate in the development of fetal right ventricular hypertrophy by studying the effects of AT1receptor blockade on cardiac growth in fetal sheep subjected to constrictive banding of the pulmonary artery (PA). Seven pairs of twin fetuses were studied beginning at 126 ± 1 days gestation (term = 145 days). One twin was given losartan (10 mg ⋅ kg−1⋅ day−1iv) for 7 consecutive days after PA banding, and the other twin served as a saline-treated, PA-banded control. Four additional pairs of twins served as sham-operated controls. Fetal heart rate (HR) and mean arterial blood pressure (MABP) were similar in the two groups of PA-banded animals before treatment and remained unchanged in the PA-banded control group. Losartan resulted in a significant decrease ( P < 0.05) in MABP between days 0 and 7, whereas HR was not affected. Total body weight of the losartan-treated animals was significantly less ( P < 0.05) than twin PA-banded controls and nonbanded fetuses. Right ventricle weight-to-body weight ratios were similar in saline (2.29 ± 0.34 g/kg) and losartan-treated (2.11 ± 0.15 g/kg) PA-banded animals and significantly greater than that in nonbanded fetuses (1.52 ± 0.07 g/kg). Similar differences were seen in the right ventricle weight-to-left ventricle weight ratios. Right and left ventricle AT1receptor mRNA and protein expression were also similar among the three groups, as were AT2receptor mRNA levels. These data suggest that endogenous angiotensin II does not contribute to the development of pressure overload-induced right ventricular hypertrophy during fetal life and that expression of angiotensin receptors is not altered by increased afterload in the ovine fetus.

Dynamic changes of gene expression in hypoxia-induced right ventricular hypertrophy

2004 ◽  
Vol 286 (3) ◽  
pp. H1185-H1192 ◽  
Author(s):  
Saumya Sharma ◽  
Heinrich Taegtmeyer ◽  
Julia Adrogue ◽  
Peter Razeghi ◽  
Shiraj Sen ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Right Ventricular ◽  
Pyruvate Dehydrogenase ◽  
Hypobaric Hypoxia ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Pyruvate Dehydrogenase Kinase ◽  
Myosin Isoforms ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
The Right

Hypobaric hypoxia induces right ventricular hypertrophy. The relative contribution of pulmonary hypertension, decreased arterial oxygen, and neuroendocrine stimulation to the transcriptional profile of hypoxia-induced right ventricular hypertrophy is unknown. Whereas both ventricles are exposed to hypoxia and neuroendocrine stimulation, only the right ventricle is exposed to increased load. We postulated that right ventricular hypertrophy would reactivate the fetal gene transcriptional profile in response to increased load. We measured the expression of candidate genes in the right ventricle of rats exposed to hypobaric hypoxia (11% O2) and compared the results with the left ventricle. Hypoxia induced right ventricular hypertrophy without fibrosis. In the right ventricle only, atrial natriuretic factor transcript levels progressively increased starting at day 7. Metabolic genes were differentially regulated, suggesting a substrate switch from fatty acids to glucose during early hypoxia and a switch back to fatty acids by day 14. There was also a switch in myosin isogene expression and a downregulation of sarcoplasmic/endoplasmic ATPase 2a during early hypoxia, whereas later, both myosin isoforms and SERCA2a were upregulated. When the right and left ventricle were compared, the transcript levels of all genes, except for myosin isoforms and pyruvate dehydrogenase kinase-4, differed dramatically suggesting that all these genes are regulated by load. Our findings demonstrate that hypoxia-induced right ventricular hypertrophy transiently reactivates the fetal gene program. Furthermore, myosin iso-gene and pyruvate dehydrogenase kinase-4 expression is not affected by load, suggesting that either hypoxia itself or neuroendocrine stimulation is the primary regulator of these genes.

scholarly journals Interleukin-17 aggravates right ventricular remodeling via activating STAT3 under both normoxia and hypoxia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Huang ◽  
Wei Zhang ◽  
Cai-lian Zhang ◽  
Lei Wang
Keyword(s):  
Body Weight ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Ventricular Remodeling ◽  
Weight Ratio ◽  
Right Ventricular Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
Interleukin 17 ◽  
Diagnostic Biomarker ◽  
Body Weight Ratio

Abstract Objective Proinflammatory cytokine interleukin 17 (IL-17) is involved in ventricular remodeling, mainly of the left ventricle. This study was designed to explore the role of IL-17 played in the pathogenesis of right ventricular hypertrophy (RVH), aiming to provide a novel treatment target or diagnostic biomarker options for improving the care of RVH patients. Methods C57BL/6 mice were maintained in 10% O2 chamber or room air for four weeks. Right ventricular hypertrophy index (RVHI), RV/body weight ratio, pulmonary arteriolar remodeling determined by percent media thickness (%MT), and the cardiomyocyte diameter of RV were evaluated. Mice were treated with exogenous recombinant mouse IL-17 (rmIL-17, 1 μg per dose twice a week) for four weeks. H9c2 cardiomyocytes were cultured and treated with IL-17 (10 ng/mL) and STAT3 inhibitor (10 ng/mL) either under normoxia (21% O2, 5% CO2, 74% N2) or under hypoxia (3% O2, 5% CO2, 92% N2). Cardiomyocyte viability was assessed by Cell counting kit 8 (CCK-8) assay. The mRNA level was detected by RT-PCR, where as the protein expression was measured by Western blot, immunohistochemistry, and immunofluorescent analyses. Results In vivo experiments showed that IL-17 did not affect the pulmonary artery under normoxia, after treatment with rmIL-17, %MT was not changed, while RVHI and the RV/body weight ratio were increased, indicating that IL-17 directly induced right ventricular hypertrophy. In a time-course study, the mice were exposed to hypoxia for 0, 1, 2, 3, 4 weeks, respectively. We found that the expression of IL-17 was gradually upregulated in RV tissue in a time-dependent manner after one week of hypoxia exposure, especially at the third and fourth week. Cardiomyocyte hypertrophy and apoptosis were observed after the exposure of the mice to hypoxia for four weeks, rmIL-17 further aggravated the hypoxia-induced cardiomyocyte hypertrophy and apoptosis. The expression of p-STAT3 in the IL-17-deficient mice was lower than in the wild-type mice. In vitro, IL-17 inhibited cardiomyocyte viability and induced cardiomyocyte apoptosis via STAT3 under both normoxic and hypoxic conditions. Conclusions These findings support a role for IL-17 as a mediator in the pathogenesis RVH, which might be considered as a potential novel anti-inflammation therapeutic strategy or diagnostic biomarker for RVH.

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