VHL gene methylation contributes to excessive erythrocytosis in chronic mountain sickness rat model by upregulating the HIF-2α/EPO pathway

Life Sciences ◽  
2021 ◽  
Vol 266 ◽  
pp. 118873
Author(s):  
Min Yang ◽  
Mingming Zhu ◽  
Kang Song ◽  
Tanna Wuren ◽  
Jun Yan ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aihaidan Abudouwayiti ◽  
Yiliyaer Nijiati ◽  
Xiangyang Zhang ◽  
Dilinuer Maimaitiyiming ◽  
Ainiwaer Aikemu

AbstractTo use isobaric tags for relative and absolute quantification (iTRAQ) technology to study the pathogenesis of chronic mountain sickness (CMS), identify biomarkers for CMS, and investigate the effect of total flavones of Dracocephalum moldavica L. (TFDM) on a rat model of CMS. We simulated high altitude hypobaric hypoxia conditions and generated a rat model of CMS. Following the administration of TFDM, we measured the pulmonary artery pressure and serum levels of hemoglobin (Hb), the hematocrit (Hct), and observed the structure of the pulmonary artery in experimental rats. Furthermore, we applied iTRAQ-labeled quantitative proteomics technology to identify differentially expressed proteins (DEPs) in the serum, performed bioinformatics analysis, and verified the DEPs by immunohistochemistry. Analysis showed that the pulmonary artery pressure, serum levels of Hb, and the Hct, were significantly increased in a rat model of CMS (P < 0.05). Pathological analysis of lung tissue and pulmonary artery tissue showed that the alveolar compartment had obvious hyperplasia and the pulmonary artery degree of muscularization was enhanced. Both pulmonary artery pressure and tissue morphology were improved following the administration of TFDM. We identified 532 DEPs by quantitative proteomics; gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further revealed that metabolic pathways associated with coagulation and complement play crucial roles in the occurrence of CMS. Immunohistochemistry verified that several DEPs (α-1-acid glycoprotein, collagen, fibulin, haptoglobin, PLTP, and TAGLN2) are important biological markers for CMS. Our analyses demonstrated that TFDM can improve CMS and exert action by influencing the metabolic pathways associated with coagulation and complement. This process relieves pulmonary artery pressure and improves lung function. We also identified that α-1-acid glycoprotein, collagen, fibulin, haptoglobin, PLTP, and TAGLN2 may represent potential biomarkers for CMS.


2014 ◽  
Vol 10 (40) ◽  
pp. 477 ◽  
Author(s):  
Ainiwaer Aikemu ◽  
Xiangyang Zhang ◽  
ShiWen Hui ◽  
Dilinuer Maimaitiyiming ◽  
Guangmei Hu

2021 ◽  
Vol 141 ◽  
pp. 111802
Author(s):  
Yiliyaer Nijiati ◽  
Tao Yang ◽  
Mutalifu Aimaiti ◽  
Dilinuer Maimaitiyiming ◽  
Ainiwaer Aikemu

2015 ◽  
Vol 61 (09/2015) ◽  
Author(s):  
Wanglei ◽  
Dilinuer Maimaitiyimin ◽  
Yang Tao ◽  
Wenhui Shi ◽  
Halmurat Upur ◽  
...  

Author(s):  
Andrew R. Steele ◽  
Michael M. Tymko ◽  
Victoria L. Meah ◽  
Lydia L Simpson ◽  
Christopher Gasho ◽  
...  

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed N-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP), in Andean males without (n=14; age=39±11) and with (n=10; age=40±12) CMS at 4330 meters (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8±7.9 vs. CMS: 8.7±5.4 ng/ml; p=0.025) and plasma aldosterone concentration (non-CMS: 77.5±35.5 vs. CMS: 54.2±28.9 pg/ml; p=0.018) were lower in highlanders with CMS compared to non-CMS, while NT pro-BNP was not different between groups (non-CMS: 1394.9±214.3 vs. CMS: 1451.1±327.8 pg/ml; p=0.15). Highlanders had similar total blood volume (non-CMS: 90±15 vs. CMS: 103±18 ml • kg-1; p=0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46±10 vs. CMS 66±14 ml • kg-1; p<0.01) and smaller plasma volume (non-CMS 43±7 vs. CMS 35±5 ml • kg-1; p=0.03) compared to non-CMS. There were no differences in ePASP between groups (non-CMS 32±9 vs. CMS 31±8 mmHg; p=0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r=-0.66; p<0.01; non-CMS: r=-0.60; p=0.022; CMS: r=-0.63; p=0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high-altitude, causing potentially greater polycythemia and clinical symptoms.


Author(s):  
Ingrid Asmussen ◽  
Luciano Bernardi ◽  
Peter Bärtsch ◽  
Tom Hornbein ◽  
Fabiola Leon-Velarde ◽  
...  

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Daniela Bermudez ◽  
Cecilia Anza‐Ramirez ◽  
Miguel Ángel Orrego‐Solano ◽  
Cristina Guerra‐Giraldez ◽  
Francisco C. Villafuerte

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