1.Internal relationship between Hippo pathway and pulmonary hypertension
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(11):1376-1380
Pulmonary hypertension is a kind of progressive pulmonary vascular diseases in which there is excessive vasoconstriction and abnormal pulmonary vascular remodeling, and then a gradual increase in pulmonary arterial pressure, and it eventually leads to right ventricular failure and even death. The pathogenesis of pulmonary hypertension is still uncertain, but some studies suggest that Hippo pathway or some components of the Hippo pathway may be involved in the progress of pulmonary hypertension. In this review, we describe the mechanism of the Hippo pathway or some components of the Hippo pathway in the progress of pulmonary hypertension.
Pulmonary hypertension
;
Hippo pathway
;
pulmonary vascular remodeling
;
review
2.Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension.
Jing CAO ; Jia-Yuan LUO ; Dian WU ; Qian ZHAO ; Ming-Xia LI
Chinese Journal of Contemporary Pediatrics 2021;23(1):103-110
OBJECTIVE:
To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV).
METHODS:
A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (
RESULTS:
The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point (
CONCLUSIONS
Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.
Animals
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Animals, Newborn
;
Hypertension, Pulmonary/etiology*
;
Hypoxia
;
Pulmonary Artery
;
Rats
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Rats, Wistar
;
Vascular Endothelial Growth Factor A
;
Vascular Remodeling
3.Progress in research of molecular mechanisms of pulmonary arterial smooth muscle cell proliferation.
Yuanyuan WU ; Guizuo WANG ; Manxiang LI
Journal of Southern Medical University 2013;33(12):1852-1855
Pulmonary hypertension (PAH) is a common clinical syndrome characterized by elevated pulmonary arterial pressure. The pathological changes in PAH include increased vasoconstrictor tone, thrombosis in situ and pulmonary vascular remodeling. Pulmonary arterial smooth muscle cell (PASMC) proliferation is a hallmark of pulmonary vascular remodeling, and exploration of the molecular mechanisms of PASMC proliferation and intervention of the involved signaling pathways is therefore of great importance for prevention and treatment of PAH. This review focus primarily on the current understanding of the molecular mechanisms involved in the proliferation of PASMCs.
Cell Proliferation
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Humans
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Hypertension, Pulmonary
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Lung
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Myocytes, Smooth Muscle
;
cytology
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Pulmonary Artery
;
cytology
;
Signal Transduction
;
Vascular Remodeling
4.Advances in molecular mechanism of vascular remodeling in pulmonary arterial hypertension.
Journal of Zhejiang University. Medical sciences 2019;48(1):102-110
Pulmonary arterial hypertension (PAH) is a clinical hemodynamic syndrome characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance leading to right heart failure and death. Vascular remodeling is the most prominent histopathological feature of PAH, which is regulated by many factors. Endoplasmic reticulum stress, calcium disorder and mitochondrial dysfunction are involved in the vascular cell proliferation and apoptosis by regulating intracellular calcium homeostasis and cellular metabolism. Epigenetic phenomenon such as DNA damage and abnormal expression of miRNA are also involved in the regulation of abnormal proliferation of vascular cells. Vascular cell phenotype switching including endothelial-mesenchymal transition and smooth muscle cell phenotype switching play an important role in abnormal proliferation of vascular cells. Vascular remodeling is produced by a variety of cells and molecular pathways, and aiming at multiple targets which is expected to find a new breakthrough in the treatment of PAH,and to improve abnormal vascular remodeling, delay or even reverse the progression of PAH.
Cell Proliferation
;
Cells, Cultured
;
Humans
;
Hypertension, Pulmonary
;
physiopathology
;
MicroRNAs
;
genetics
;
Myocytes, Smooth Muscle
;
pathology
;
Pulmonary Artery
;
pathology
;
Vascular Remodeling
;
genetics
5.Role of myelin and lymphocyte protein in regulating pulmonary artery smooth muscle cell proliferation and apoptosis in pulmonary hypertension.
Jin Jun LIU ; Qing Qing LI ; Chao Chao ZENG ; Yue Xiang WANG ; Qing Tian HU ; Hong Ju WANG ; Shi Li WU
Journal of Southern Medical University 2022;42(10):1572-1577
OBJECTIVE:
To investigate the role of myelin and lymphocyte protein (MAL) in pulmonary hypertension (PAH).
METHODS:
Blood samples were collected from 50 patients with PAH (PAH group) and 50 healthy individuals for detection of plasma MAL expression using ELISA.According to the echocardiographic findings, the patients were divided into moderate/severe group (n=18) and mild group (n=32), and the correlation between MAL protein level and the severity of PAH was analyzed.In a pulmonary artery smooth muscle cell model of PAH with hypoxia-induced abnormal proliferation, the effects of mal gene knockdown and overexpression on cell growth, proliferation and starvation-induced apoptosis were observed; the changes in NK-κB signaling pathway in the transfected cells were detected to explore the molecular mechanism by which MAL regulates PAMSC proliferation and apoptosis.
RESULTS:
The plasma level of MAL was significantly higher in patients with PAH than in healthy individuals (P < 0.05), and the patients with moderate/severe PAH had significantly higher MAL level than those with mild PAH (P < 0.001).In PAMSCs, exposure to hypoxia significantly increased the mRNA and protein expression levels of MAL (P < 0.05), and MAL knockdown obviously inhibited hypoxia-induced proliferation and promoted starvation-induced apoptosis of the PAMSCs (P < 0.05).Knocking down mal significantly inhibited the activation of NK-κB signaling pathway that participated in regulation of PAMSC proliferation (P < 0.05).
CONCLUSION
The plasma level of MAL is elevated in PAH patients in positive correlation with the disease severity.MAL knockdown inhibits abnormal proliferation and promotes apoptosis of PAMSCs by targeted inhibition of the NF-κB signaling pathway to improve vascular remodeling in PAH.
Humans
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Pulmonary Artery
;
Hypertension, Pulmonary
;
Myelin Sheath/metabolism*
;
Apoptosis
;
Myocytes, Smooth Muscle
;
Vascular Remodeling/genetics*
;
Cell Proliferation
;
Hypoxia/metabolism*
;
Lymphocytes
6.Clinicopathological analysis of pulmonary vascular disease in 38 neonates died of respiratory failure.
Ning LI ; Hong-Wu CHEN ; Xin-Hua ZHOU ; Li LIANG
Journal of Southern Medical University 2016;37(4):528-532
We reviewed the data of 38 neonates who died of respiratory failure. Paraffin sections of the autopsy lung samples were examined with HE staining or immunolabeling for CD34, CD68 and CK to observe the development of the pulmonary vessels and detect potential pulmonary vascular diseases (PVDs). Five cases were identified to have PVDs, including pulmonary hypertensive vascular remodeling in 3 cases and alveolar capillary dysplasia in 2 cases. The result indicated that PVD was one of the important reasons for respiratory failure in these neonates.
Death
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Humans
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Infant, Newborn
;
Lung
;
pathology
;
Lung Diseases
;
diagnosis
;
Persistent Fetal Circulation Syndrome
;
pathology
;
Pulmonary Alveoli
;
abnormalities
;
pathology
;
Respiratory Insufficiency
;
mortality
;
Vascular Diseases
;
diagnosis
;
Vascular Remodeling
7.Effect of heat shock protein 70 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension.
Kun-Zhen LIU ; Le WANG ; Ming-Xia LI
Chinese Journal of Contemporary Pediatrics 2016;18(2):152-158
OBJECTIVETo investigate the effect of heat shock protein 70 (HSP70) on pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).
METHODSA total of 128 Wistar neonatal rats were randomly divided into HPH model and blank control groups. According to the transfection solution, the HPH model group was further divided into normal saline group, empty virus group (viral vectors marked with a green fluorescent signal and not carrying the target gene), and virus+HSP70 group (viral vectors marked with a green fluorescent signal and carrying the target gene). The HPH model was established by inhalation of nitrogen-oxygen mixture (1.5 L/minutes and 8% oxygen). Pulmonary arterial pressure (mPAP) and the indicators of pulmonary vascular remodeling (MT% and MA%) were measured on days 3, 7, 10, and 14 of hypoxia.
RESULTSOn days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups had significantly enhanced expression of HSP70 compared with the blank control group (P<0.01), and the virus+HSP70 group had significantly higher expression of HSP70 than the blank control, normal saline, and empty virus groups (P<0.01). On day 14 of hypoxia, the expression of HSP70 showed no significant difference between these groups (P>0.05). On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups showed continuous increases in mPAP compared with the blank control group (P<0.05). There was no significant difference in mPAP between the virus+HSP70 and blank control groups (P>0.05). On day 14 of hypoxia, there was no significant difference in mPAP among three subgroups of the HPH model group (P>0.05), but the mPAP in the three subgroups was significantly higher than in the blank control group (P<0.05). After 7 days of hypoxia, the normal saline and empty virus groups showed significantly higher MT% and MA% than the blank control group (P<0.05), but the two indicators showed no significant differences between the virus+HSP70 and the blank control groups (P>0.05). On day 14 of hypoxia, there were no significant differences in MT% and MA% among three subgroups of the HPH model group (P>0.05), but the MT% and MA% in the three subgroups were higher than in the blank control group (P<0.05).
CONCLUSIONSHSP70 may reduce pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with HPH.
Animals ; HSP70 Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Hypertension, Pulmonary ; cerebrospinal fluid ; metabolism ; physiopathology ; Hypoxia ; genetics ; metabolism ; physiopathology ; Oxygen ; metabolism ; Pulmonary Artery ; metabolism ; Rats ; Rats, Wistar ; Vascular Remodeling
8.Research progress on the mechanism of phenotypic transformation of pulmonary artery smooth muscle cells induced by hypoxia.
Journal of Zhejiang University. Medical sciences 2023;51(6):750-757
Phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) is a key factor in pulmonary vascular remodeling. Inhibiting or reversing phenotypic transformation can inhibit pulmonary vascular remodeling and control the progression of hypoxic pulmonary hypertension. Recent studies have shown that hypoxia causes intracellular peroxide metabolism to induce oxidative stress, induces multi-pathway signal transduction, including those related to autophagy, endoplasmic reticulum stress and mitochondrial dysfunction, and also induces non-coding RNA regulation of cell marker protein expression, resulting in PASMCs phenotypic transformation. This article reviews recent research progress on mechanisms of hypoxia-induced phenotypic transformation of PASMCs, which may be helpful for finding targets to inhibit phenotypic transformation and to improve pulmonary vascular remodeling diseases such as hypoxia-induced pulmonary hypertension.
Humans
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Pulmonary Artery
;
Hypertension, Pulmonary
;
Vascular Remodeling/genetics*
;
Hypoxia/genetics*
;
Myocytes, Smooth Muscle
;
Cell Proliferation/physiology*
;
Cells, Cultured
;
Cell Hypoxia/genetics*
9.Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism.
Xin GUO ; Ming-Xia LI ; Caicike BAYER ; Yan-Qing YANG ; Le WANG
Chinese Journal of Contemporary Pediatrics 2023;25(4):407-414
OBJECTIVES:
To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).
METHODS:
A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.
RESULTS:
The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).
CONCLUSIONS
Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.
Rats
;
Animals
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Hypertension, Pulmonary
;
Becaplermin
;
Animals, Newborn
;
Proliferating Cell Nuclear Antigen
;
Vascular Remodeling
;
Pulmonary Artery/metabolism*
;
Hypoxia
;
Oxygen
;
Cell Proliferation
;
Myocytes, Smooth Muscle/metabolism*
10.Hemoptysis during general anesthesia in a diabetic patient with healed tuberculosis: a case report.
Mee Young CHUNG ; Hyeon Do JEONG ; Seul Gi KIM ; Chang Jae KIM
Korean Journal of Anesthesiology 2017;70(1):86-89
Hemoptysis is a common complication of pulmonary tuberculosis. Most of the cases of hemoptysis originate from hypertrophied bronchial arteries. Also, diabetes induces pulmonary vascular abnormalities such as endothelial dysfunction, inflammatory infiltration and pulmonary vascular remodeling. A 27-year-old male, with diabetes and a history of tuberculosis, underwent the procedure of pars plana vitrectomy under general anesthesia. After an uneventful intra-operative period, he had hemoptysis prior to extubation. Emergency fiberoptic bronchscopy showed blood plugs and spotted fresh blood at the right upper lobar bronchus. After successful embolization of the bronchial artery, the patient made a recovery and was discharged without experiencing any complication. Predisposing factors of hemoptysis in this case are presumed to be tuberculosis and diabetes. The bleeding might had been caused by the rupture of a weakened artery within the cavity in the right upper lobe, through expansion of the lung during manual ventilation by positive pressure.
Adult
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Anesthesia, General*
;
Arteries
;
Bronchi
;
Bronchial Arteries
;
Causality
;
Diabetes Mellitus
;
Emergencies
;
Hemoptysis*
;
Hemorrhage
;
Humans
;
Lung
;
Male
;
Rupture
;
Tuberculosis*
;
Tuberculosis, Pulmonary
;
Vascular Remodeling
;
Ventilation
;
Vitrectomy