The role of endogenous carbon monoxide in the hypoxic vascular remodeling of rat model of hypoxic pulmonary hypertension

2003 ◽  
Vol 23 (4) ◽  
pp. 356-358 ◽  
Author(s):  
Zhen Guohua ◽  
Zhang Zhenxiang ◽  
Xu Yongjian
Keyword(s):  
Carbon Monoxide ◽  
Pulmonary Hypertension ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Hypoxic Pulmonary Hypertension

scholarly journals Experimental intravascular hemolysis induces hemodynamic and pathological pulmonary hypertension: association with accelerated purine metabolism

2018 ◽  
Vol 8 (3) ◽  
pp. 204589401879155 ◽  
Author(s):  
Victor P. Bilan ◽  
Frank Schneider ◽  
Enrico M. Novelli ◽  
Eric E. Kelley ◽  
Sruti Shiva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Purine Nucleoside Phosphorylase ◽  
Autologous Blood ◽  
Systolic Pressure ◽  
Per Se ◽  
Parenchymal Injury

Pulmonary hypertension (PH) is emerging as a serious complication associated with hemolytic disorders, and plexiform lesions (PXL) have been reported in patients with sickle cell disease (SCD). We hypothesized that repetitive hemolysis per se induces PH and angioproliferative vasculopathy and evaluated a new mechanism for hemolysis-associated PH (HA-PH) that involves the release of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) from erythrocytes. In healthy rats, repetitive administration of hemolyzed autologous blood (HAB) for 10 days produced reversible pulmonary parenchymal injury and vascular remodeling and PH. Moreover, the combination of a single dose of Sugen-5416 (SU, 200 mg/kg) and 10-day HAB treatment resulted in severe and progressive obliterative PH and formation of PXL (Day 26, right ventricular peak systolic pressure (mmHg): 26.1 ± 1.1, 41.5 ± 0.5 and 85.1 ± 5.9 in untreated, HAB treated and SU+HAB treated rats, respectively). In rats, repetitive administration of HAB increased plasma ADA activity and reduced urinary adenosine levels. Similarly, SCD patients had higher plasma ADA and PNP activity and accelerated adenosine, inosine, and guanosine metabolism than healthy controls. Our study provides evidence that hemolysis per se leads to the development of angioproliferative PH. We also report the development of a rat model of HA-PH that closely mimics pulmonary vasculopathy seen in patients with HA-PH. Finally, this study suggests that in hemolytic diseases released ADA and PNP may increase the risk of PH, likely by abolishing the vasoprotective effects of adenosine, inosine and guanosine. Further characterization of this new rat model of hemolysis-induced angioproliferative PH and additional studies of the role of purines metabolism in HA-PH are warranted.

scholarly journals N7-methylguanosine modification of lncRNAs in a rat model of hypoxic pulmonary hypertension: a comprehensive analysis

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Huan Wang ◽  
Ren Biao Chen ◽  
Si Ni Zhang ◽  
Rui Feng Zhang
Keyword(s):  
Pulmonary Hypertension ◽  
Clinical Significance ◽  
Rat Model ◽  
Critical Role ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Hypoxic Pulmonary Hypertension ◽  
Non Coding Rnas ◽  
First Time

Abstract Background Long non-coding RNAs (lncRNAs) play a critical role in the pathogenesis of hypoxic pulmonary hypertension (HPH). The role of N7-methylguanosine (m7G) modification in lncRNAs has received increased attentions in recent years. However, the m7G-methylation of lncRNA in HPH has yet to be determined. We have therefore performed a transcriptome-wide analysis of m7G lncRNAs in HPH. Results Differentially-expressed m7Gs were detected in HPH, and m7G lncRNAs were significantly upregulated compared with non-m7G lncRNAs in HPH. Importantly, this was the first time that the upregulated m7G lncXR_591973 and m7G lncXR_592398 were identified in HPH. Conclusion This study provides the first m7G transcriptome-wide analysis of HPH. Importantly, two HPH-associated m7G lncRNAs were identified, although their clinical significance requires further validation.

scholarly journals The role of ATG-7 contributes to pulmonary hypertension by impacting vascular remodeling

2021 ◽  
Author(s):  
Xi Yang ◽  
Li Zhang ◽  
Jian-qiang Ye ◽  
Xiao-hui Wu ◽  
Xi-xi Zeng ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling

scholarly journals The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes

2015 ◽  
Vol 308 (3) ◽  
pp. L229-L252 ◽  
Author(s):  
Steven C. Pugliese ◽  
Jens M. Poth ◽  
Mehdi A. Fini ◽  
Andrea Olschewski ◽  
Karim C. El Kasmi ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Signaling Pathways ◽  
Vascular Remodeling ◽  
Mesenchymal Cells ◽  
World Health ◽  
Small Subset ◽  
Cellular Interactions ◽  
Pulmonary Vascular Remodeling ◽  
Hypoxic Pulmonary Hypertension ◽  
Group I

Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop “out-of-proportion” severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines (“second hit”) antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease.

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