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1.
Chinese Pharmacological Bulletin ; (12): 62-69, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1013591

RESUMO

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

2.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 114-120, 2023.
Artigo em Chinês | WPRIM | ID: wpr-1014706

RESUMO

Pulmonary hypertension (PH) is a rare and severe progressive disease. It results from hypertrophic remodeling of distal pulmonary arterioles that increases pulmonary arterial pressure and pulmonary vascular resistance in the absence of left heart, pulmonary parenchymal, or thromboembolic disease. Hypoxia-inducible factor-1 (HIF-1) regulates a large number of genes related to the occurrence and development of PH, and induces pulmonary angiogenesis, cell proliferation and migration, cellular energy metabolism and utilization. HIF-1 is an important component of the pathogenesis of hypoxic PH and plays an important role in driving the pathological process of pulmonary vascular and right ventricular remodeling. This article systematically elucidated the role and regulation of HIF-1 in hypoxic PH and its potential in targeted therapy of PH.

3.
Journal of Zhejiang University. Medical sciences ; (6): 750-757, 2023.
Artigo em Inglês | WPRIM | ID: wpr-971092

RESUMO

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.


Assuntos
Humanos , Artéria Pulmonar , Hipertensão Pulmonar , Remodelação Vascular/genética , Hipóxia/genética , Miócitos de Músculo Liso , Proliferação de Células/fisiologia , Células Cultivadas , Hipóxia Celular/genética
4.
Acta Pharmaceutica Sinica B ; (6): 2369-2382, 2023.
Artigo em Inglês | WPRIM | ID: wpr-982871

RESUMO

Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

5.
Clinics ; 77: 100051, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1384603

RESUMO

Abstract Objectives Some previous studies indicated that the excessive proliferation and migration of Pulmonary Artery Smooth Muscle Cells (PASMCs) could be observed in pulmonary artery intima after Pulmonary Embolism (PE) occurred. In addition, recent studies identified some miRNAs that are differentially expressed in the blood of PE patients, which might be used as a diagnostic biomarker for PE, including let-7a-5p, let-7b-5p, and miR-150-5p. Hence, the authors sought to explore the effects of let-7b-5p in PASMC proliferation and migration and the corresponding regulatory mechanism. Methods Platelet-Derived Growth Factor (PDGF) was utilized to induce the hyper-proliferation model in PASMCs. The mRNA and protein expression levels were detected by RT-qPCR and western blot, respectively. The proliferation of PASMCs was evaluated by the detection of PCNA expression, as well as CCK-8 and Edu assays. Wound healing and Transwell assays were exploited to assess the migration ability of PASMCs. The targets of let-7b-5p were predicted based on two bioinformatics online tools. Dual-luciferase and Ago2 pull-down assays were applied to confirm the interaction between let-7b-5p and IGF1. Results 40 ng/mL PDGF was selected as the optimal concentration to induce PASMCs. let-7b-5p mimics suppressed the proliferation and migration of PDGF-induced PASMCs, while let-7b-5p inhibitor led to the opposite result. In further mechanism exploration, IGF1 was predicted and confirmed as the direct target gene of let-7b-5p. The promotion role of IGF1 overexpression on the proliferation and migration of PDGF-induced PASMCs was dramatically countered by let-7b-5p mimics. Conclusion let-7b-5p prohibits the proliferation and migration of PDGF-induced PASMCs by modulating IGF1.

6.
Chinese Pharmacological Bulletin ; (12): 506-511, 2022.
Artigo em Chinês | WPRIM | ID: wpr-1014110

RESUMO

Pulmonary hypertension ( PH) is occult, with no distinctive clinical manifestations and poor prognosis.Pulmonary vascular remodelling is an important pathological feature in which pulmonary artery smooth muscle cell ( PASMCs) pheno- typic switching plays a crucial role.MicroRNA (miRNA) is a class of evolutionary highly conserved single-stranded small non-coding RNA.Recently, an increasing number of scholars have found that miRNA can play an important role in the occurrence and development of PH by regulating the phenotypic switching of PASMCs, which is expected to be a potential target for the prevention and treatment of PH.It has been found that miR NA such as miR-221 , miR-24, miR-15b, miR-96, miR-23a.miR-9, miR-214, miR-20a can promote the phenotypic switching of PASMCs, while miRNA such as miR-21, miR-132, miR-182, miR-449, miR-206 .miR-124, miR-30c, miR-140.miR-17-92 cluster can inhibit it.This article aims to review the research progress on miRNA that mediates PASMCs phenotypic switching in PH from both growth factor-related miRNA and hy- poxia-related miRNA.

7.
Chinese Pharmacological Bulletin ; (12): 492-496, 2022.
Artigo em Chinês | WPRIM | ID: wpr-1014107

RESUMO

Chronic hypoxic lung diseases are major causes of disability and mortality worldwide, which are typically aggravated by hypoxic pulmonary hypertension.The pathogenesis of hypoxic pulmonary hypertension is complex, and its mechanism has not been fully elucidated.The previous studies have shown abnormally elevated levels of free Ca + in the cytoplasm of pulmonary artery smooth muscle cells to be the predominant drivers of pulmonary hypertension , causing continuous contraction and remodeling of the pulmonary vessels.This article briefly summarizes the mechanism of hypoxia-induced imbalance in calcium homeostasis in pulmonary artery smooth muscle cells, together with its related drug research, based on the existing literature.Hypoxia induces an imbalance in calcium homeostasis in pulmonary artery smooth muscle cells by regulating hypoxia-inducible factor-1, K+ , store-operated calcium channel, receptor-operated calcium channel, the Ca +-sensing myosin contractile mechanism by binding to calmodulin, leading to pulmonary vasoconstriction.Ca + can also activate PKC/ MAPKs and PI3K/Akt/mTOR pathways, leading to pulmonary vascular remodeling.

8.
China Journal of Chinese Materia Medica ; (24): 1024-1030, 2022.
Artigo em Chinês | WPRIM | ID: wpr-928022

RESUMO

This study investigated the effect of salidroside on phenotypic transformation of rat pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia. Rat pulmonary arteries were isolated by tissue digestion and PASMCs were cultured. The OD values of cells treated with salidroside at different concentrations for 48 hours were measured by cell counting kit-8(CCK-8) to determine the appropriate concentration range of salidroside. The cells were divided into a normal(normoxia) group, a model(hypoxia) group, and three hypoxia + salidroside groups(40, 60, and 80 μg·mL~(-1)). Quantitative real-time PCR(qRT-PCR) was used to detect the mRNA expression of cell contractile markers in each group, such as α-smooth muscle actin(α-SMA), smooth muscle 22(SM22), and calcium-binding protein(calponin), and synthetic marker vimentin. The expression levels of cell phenotypic markers and proliferating cell nuclear antigen(PCNA) were detected by Western blot. The proliferation of cells in each group was detected by the 5-ethynyl-2'-deoxyuridine(EdU) assay. Cell migration was measured by Transwell assay. As revealed by results, compared with the normal group, the model group showed decreased mRNA and protein expression of contractile phenotypic markers of PASMCs and increased mRNA and protein expression of synthetic markers. Compared with the conditions in the model group, salidroside could down-regulate the mRNA and protein expression of synthetic markers in PASMCs and up-regulated the mRNA and protein expression of contractile phenotypic markers. Compared with the normal group, the model group showed potentiated proliferation and migration. Compared with the model group, the hypoxia + salidroside groups showed blunted proliferation and migration of cells after phenotypic transformation. The results suggest that salidroside can inhibit the expression of synthetic markers in PASMCs and promote the expression of contractile markers to inhibit the hypoxia-induced phenotypic transformation of PASMCs. The mechanism of salidroside in inhibiting the proliferation and migration of PASMCs is related to the inhibition of the phenotypic transformation of PASMCs.


Assuntos
Animais , Ratos , Proliferação de Células , Células Cultivadas , Glucosídeos , Hipóxia , Miócitos de Músculo Liso , Fenóis , Artéria Pulmonar
9.
China Pharmacy ; (12): 1337-1344, 2021.
Artigo em Chinês | WPRIM | ID: wpr-877255

RESUMO

OBJECTIVE:To investigate the effects and mechanism of puerarin (Pue) on hypoxia-induced pyroptosis of pulmonary artery smooth muscle cells (PASMCs). METHODS :PASMCs of rats as research objects were randomly divided into normoxia group ,hypoxia group and hypoxia+Pue group (0.2 mmol/L). Except for normoxia group ,other groups were cultured with 5% CO2 and 3% O2 at 37 ℃ for 24 hours to establish hypoxia model. Western blot assay was used to detect the expression of pyroptosis related proteins [NOD-like receptor protein- 3 (NLPR3),caspase-1,interleukin-1 β (IL-1 β),apoptosis-associated speck-like protein (ASC)]. Lactate dehydrogenase (LDH)release assay was used to detect the release of LDH in cells ;Hoechst 33342/PI double staining test was adopted to detect the proportion of pyroptosis positive cells. PASMCs was randomly divided into normoxia group+control plasmid group ,hypoxia+control plasmid group ,hypoxia+over-expression plasmid group and hypoxia+ over-expression plasmid+Pue group. Except for the normoxia+control plasmid group ,the other groups were established hypoxia model by the same method. After transfection of control plasmid or NLRP 3 over-expression plasmid ,Western blot ,LDH release test and Hoechst 33342/PI double staining test were used to investigate whether Pue could inhibit hypoxia-induced PASMCs pyroptosis by interfering with the activity of NLRP 3 inflammasomes. RESULTS :Compared with normoxia group ,the expression of pyroptosis related proteins ,the release of LDH and the proportion of pyroptosis positive cells were increased significantly in hypoxia group (P<0.05 or P<0.01). Pue had the effect of reversing the above indexes (P<0.05 or P<0.01). When the NLRP 3 inflammasome was over-expressed ,the expression of pyroptosis related proteins ,the release of LDH and the proportion of Δ 基金项目:黑龙江省自然科学基金资助项目(No.ZD201416) pyroptosis positive cells were increased significantly (P<0.05 *教授,博士生导师 ,博士。研究方向 :心血管药理学 。电话: or P<0.01). Pue could inhibit the above phenomenon through 0451-58853046。E-mail:zhangxd85@163.com regulating NLRP 3 inflammasome (P<0.05 or P<0.01). 中国药房 2021年第32卷第11期 China Pharmacy 2021Vol. 32 No. 11 ·1337· CONCLUSIONS:Pue can significantly inhibit the hypoxia-induced pyroptosis of PASMCs by down-regulating the expression of pyroptosis related proteins ,reducing the release of LDH and proportion of pyroptosis positive cells. The mechanism is related to the activity inhibition of NLRP 3 inflammasome.

10.
J Biosci ; 2020 Feb; : 1-9
Artigo | IMSEAR | ID: sea-214327

RESUMO

This paper explores the potential mechanism of microRNA-143–5p regulation effects on pulmonary arterysmooth muscle cells (PASMCs) functions in hypoxic pulmonary hypertension (HPH) via targeting HIF-1a,which may offer a new idea for HPH therapy. PASMCs were transfected with mimics control/miR-143–5pmimics or inhibitor control/miR-143–5p inhibitor. We used Western blotting and RT-qPCR to detect the proteinand mRNA expressions, CCK-8 assay to detect cellular viability, Annexin V-FITC/PI staining and caspase3/cleaved caspase-3 protein to evaluate cellular apoptosis, transwell migration experiment for cellularmigration measurement and Dual luciferase reporter gene assay to prove the target of miR-143–5p. Cells underhypoxic condition presented the decreased protein and mRNA expressions of a-smooth muscle actin (SM-aactin), Myocardin, smooth muscle myosin heavy chain (SMMHC), and smooth muscle-22a (SM22a),Calponin1 and Hypoxia-inducible factor-1a(HIF-1a), the increased cell viability and miR-143–5p level; Overexpression of miR-143–5p obviously reduced vascular smooth muscle-specific contraction marker proteinlevels and cellular apoptosis, increased cellular migration of PASMCs with hypoxia stimulation; Low-expression of miR-143–5p caused the opposite changes, while co-transfected with Si HIF-1a blocked thebeneficial effects of miR-143–5p inhibition on PASMCs under hypoxia. MicroRNA-143–5p can promote thephenotype conversion, proliferation and migration of pulmonary artery smooth muscle cells under hypoxiccondition through direct targeting of HIF-1a.

11.
Chinese Circulation Journal ; (12): 1118-1123, 2018.
Artigo em Chinês | WPRIM | ID: wpr-703937

RESUMO

Objectives: To explore the effect of 17β-estradiol (E2) on hypoxic pulmonary hypertension (HPH) and explore if the effects were mediated through suppressing pulmonary artery smooth muscle cells (PASMCs) proliferation by targeting miRNA-21 (miR-21). Methods: Animal experiment: A total of 32 healthy female SD rats with castrated surgery were randomly divided into 4 groups: normoxia group, normoxia+E2 group, hypoxia group, hypoxia+E2 group (n=8 each). The rats in normoxia+E2 group and hypoxia+E2 group received subcutaneous injection of E2 20 μg/kg/d, and the rest groups received subcutaneous injection of equal volume saline. The hypoxic groups were placed in the hypoxic chamber (24 hours per day for 8 weeks) to establish HPH model and normoxic groups were kept in the room air. The pulmonary artery remodeling, mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI) were observed. Real-time PCR and Western blot were used to detect the levels of proliferation cell nuclear antibody (PCNA) and miR-21 expression in pulmonary artery. In vitro: human pulmonary artery smooth muscle cells (hPASMCs) were randomly divided into 3 groups: normoxia group, hypoxia group, hypoxia+E2 group. The levels of cell proliferation in each group were tested by MTT after 24 hours. Real-time PCR and Western blot were used to detect the levels of PCNA and miR-21 in cells. Results: Animal experiment: compared with normoxia group, the hypoxia group showed obviously thickened pulmonary artery wall, increased mPAP and RVHI, and significantly increased expression of miR-21 and PCNA (P<0.01);above changed were significantly attenuated in hypoxia+E2 group (P<0.01). In vitro: compared with normoxia group, the hypoxia group showed obvious proliferation and significantly increased expression of miR-21 and PCNA (P<0.01);compared with hypoxia group, the proliferation of hPASMCs and expression of miR-21 and PCNA were obviously reduced in hypoxia+E2 group (P<0.01). Conclusions: E2 could effectively reduce mPAP, attenuate the degree of right heart hypertrophy and pulmonary vascular remodeling, the protective effect may be mediated through downregulating miR-21 and PCNA expression, and subsequently inhibiting the proliferation of hPASMCs.

12.
Chinese Journal of Pharmacology and Toxicology ; (6): 89-98, 2018.
Artigo em Chinês | WPRIM | ID: wpr-705246

RESUMO

OBJECTIVE To explore the inhibitory effects of epalrestat (EPS) on platelet-derived growth factor (PDGF)-induced rat pulmonary artery smooth muscle cells proliferation by inhibiting aldose reductase (AR) expression.METHODS Primary rat pulmonary arterial smooth muscle cells (PASMCs) were prepared from the pulmonary artery of male 10-week-old Sprague-Dawley rats using explant method.PDGF 30 mg·L-1was given to induce cell proliferation.After PASMCs grew to 70%-80% conflu?ence, AR small-interferring RNA(ARsiRNA) was transfected with Lipofectamine 3000 into PASMCs. After 24 h,the expression and activity of AR were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR),Western blotting and spectrophotometric method,respectively to investigate EPS on PASMCs proliferation and proliferating cell nuclear antigen (PCNA) and collagenⅠexpression induced by PDGF from in vitro. PASMCs (normal control, PDGF 30 mg·L-1, PDGF+EPS 1, 10 and 100 μmol·L-1,EPS 100 μmol·L-1)were treated according to groups.Cell proliferation was measured by BrdU marking and flow cytometry. The expressions of AR, PCNA and collagenⅠwere analyzed with RT-qPCR and Western blotting.RESULTS In cultured PASMCs,compared with normal control group, the application of exogenous PDGF-induced cell proliferation concomitantly up-regulated AR expres?sion and activity (P<0.01), and such effect was abolished by ARsiRNA. Compared with PDGF group, EPS attenuated PDGF-induced proliferation of PASMCs,expression of PCNA,and collagenⅠ(P<0.05, P<0.01),and the inhibitory effect of EPS was accompanied by inhibition of AR expression(P<0.05,P<0.01).CONCLUSION EPS inhibits PDGF-induced proliferation of PASMCs via inhibiting AR expression.

13.
Chinese Pharmacological Bulletin ; (12): 664-669, 2018.
Artigo em Chinês | WPRIM | ID: wpr-705104

RESUMO

Aim To investigate the alteration of volt-age-depending potassium channel(KV) current in pul-monary arterial smooth muscle cells(PASMCs) of pul-monary hypertension (PH) rats, and the effect of tet-raethylammonium (TEA,a blocker of KV) on potassi-um channel current in different PH models. Methods The whole-cell patch clamp techniques were applied to record the KVcurrents from PASMCs cultured with Ham's F-12 (1% FBS). Furthermore, the effects of TEA on the KVcurrents were examined in different PH models. Results The whole-cell KVcurrents were ob-viously inhibited in PASMCs of chronic hypoxia (CH)and monocrotaline (MCT)-treated rats. TEA signifi-cantly decreased the whole-cell KVcurrents in PASMCs of control and PH rats,and the inhibitory effect of TEA was dramatically reduced in PH group. Conclusions The degree of the voltage-dependent potassium chan-nels opening is significantly inhibited in PASMCs of CH and MCT-treated rats,accordingly,the TEA-sen-sitive KVcurrents obviously decrease.

14.
Chinese Journal of Applied Clinical Pediatrics ; (24): 672-676, 2017.
Artigo em Chinês | WPRIM | ID: wpr-610565

RESUMO

Objective To investigate the effects of endogenous sulfur dioxide (SO2) on the oxidative stress induced by cobalt chloride (CoCl2) in the rat pulmonary artery smooth muscle cells (PASMCs).Methods Rat PASMCs were treated with 200 μ mol/L CoCl2 to mimic the hypoxia insult.Endogenous SO2 generating enzyme aspartate aminotransferase 1 (AAT1) expression was upregulated or downregulated (AAT1 sh) by transfection with lentivirus.Rat PASMCs were randomly divided into 8 groups:vehicle group,vehicle + CoCl2 group,AAT1 group,AAT1 + CoCl2 group,scramble group,scramble + SO2 group,AAT1 sh group and AAT1 sh + SO2 group.SO2 donor Na2 SO3/NaHSO3 at concentration of 100 μ mol/L were added in scramble + SO2 group and AAT1sh + SO2 group.The expressions of AAT1,superoxide dismutase 1 (SOD1) and SOD2 in PASMCs were detected by Western blot method.In situ SO2 content in PASMCs was detected by fluorescent probe.The superoxide anions in PASMCs were labeled by dihydroethidium (DHE) probe under fluorescent microscope.Results Compared with the vehicle group,the levels of SO2 and the expressions of AAT1 (0.221 ± 0.002 vs.0.446 ± 0.004),SOD1 (0.076 ± 0.028 vs.0.171 ± 0.019) and SOD2 (0.080 ± 0.031 vs.0.196 ± 0.018) significantly decreased (all P < 0.01),and superoxide anion increased in rat PASMCs of vehicle + CoCl2 group.Meanwhile,compared with vehicle + CoCl2 group,the levels of SO2 and the expressions of AAT1 (0.839 ± 0.056 vs.0.221 ± 0.002),SOD1 (0.177 ± 0.020 vs.0.076 ± 0.028) and SOD2 (0.195 ±0.018 vs.0.080-± 0.031) markedly increased (all P < 0.01),and superoxide anion decreased in rat PASMCs of AAT1 + CoCl2 group.On the contrary,compared with the scramble group,the levels of SO2 and the expressions of AAT1 (0.062 ±0.017 vs.0.354 ±0.034),SOD1 (0.054 ±0.029 vs.0.157 ±0.023) and SOD2(0.180 ±0.100 vs.0.586 ± 0.176)significantly decreased (all P < 0.01),and superoxide anion increased in rat PASMCs of AAT1sh group.Furthermore,compared with the AAT1 sh group,the levels of SO2 and the expressions of SOD1 (0.155 ± 0.022vs.0.054 ± 0.029) and SOD2 (0.578 ± 0.200 vs.0.180 ± 0.100) significantly increased (all P < 0.01),and superoxide anion decreased in rats PASMCs of AAT1sh + SO2 group.Conclusion Endogenous SO2/AAT1 inhibits CoCl2-induced oxidative stress in rat PASMCs.

15.
Chinese Pharmacological Bulletin ; (12): 768-772, 2016.
Artigo em Chinês | WPRIM | ID: wpr-493832

RESUMO

Sustained hypoxic pulmonary vasoconstriction (HPV ) as experienced at high altitude can lead to hypoxic pulmonary hypertension(HPH).HPV,a special physiological phenomenon of lung,is the physiological reflex of organism in hypoxic envi-ronment.However,in high altitude hypoxic environment,the sustained HPV can lead to pulmonary vascular remodeling and right ventricular hypertrophy,at the same time,the degree of hypoxia in alveoli can be aggravated.Vicious circle of hypoxia is formed,further causing the severe high altitude sickness such as pulmonary edema and pulmonary heart disease.HPV appears in preliminary of HPH,but in the chronic phase,irreversible hy-poxic pulmonary vascular remodeling forms.Therefore,studying the mechanism of HPV and the effect of HPV in HPH can pro-vide targets and ideas for the prevention and treatment of high al-titude sickness. Additionally, in preliminary stage of HPV, prompt treatment is critical for the prevention of high altitude sickness.However,the mechanism of HPV and its roles in HPH are still not fully elucidated in current studies.This paper sum-marizes the studies about HPV in HPH of recent years,aiming to provide references for researchers and clinical treatment in this research field.

16.
Indian J Biochem Biophys ; 2015 Apr; 52 (2): 119-124
Artigo em Inglês | IMSEAR | ID: sea-158207

RESUMO

The role of angiotensin II in regulating Na+/K+-ATPase activity has been investigated in bovine pulmonary artery smooth muscle cells (BPASMCs). Our study reveals that angiotensin II inhibits the Na+/K+ATPase activity via glutathionylation of the pump with the involvement of an increase in NADPH oxidase-derived O2.-. Additionally, angiotensin II treatment to the cells increases the inhibitory potency of the 15.6 kDa inhibitor towards the Na+/K+ATPase activity.


Assuntos
Angiotensina II/metabolismo , Inibidores Enzimáticos/química , Glutationa/farmacologia , /enzimologia , Oxirredução , Artéria Pulmonar/enzimologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/química
17.
Chongqing Medicine ; (36): 2600-2601,2605, 2015.
Artigo em Chinês | WPRIM | ID: wpr-600371

RESUMO

Objective To observe the changes of microRNA‐214 (miR‐214) expression in rat pulmonary artery smooth mus‐cle cells (PASMCs) induced by different hypoxia time ,and lay the foundation to explore the effect and mechanism of regulation of miR‐214 on PASMCs proliferation .Methods The primary cultured PASMCs were cultured under hypoxic 0 h ,6 h ,12 h ,24 h ,48 h ,respectively .The real time quantitative PCR was used to detect miR‐214 expression in each group PASMCs .Results The ex‐pression of miR‐214 in hypoxia group PASMCs was sustained as time increased ,apart from hypoxic hypoxia 6h group and 0h group ,the expression of miR‐214 was no significant difference (P>0 .05);the expression of miR‐214 among other groups PASMCs was significantly different (P<0 .05) .Conclusion The expression of miR‐214 in PASMCs increased after induction of hypoxia .We speculated that miR‐214 may be involved in the regulation of hypoxia induced PASMCs proliferation .

18.
Basic & Clinical Medicine ; (12): 1303-1307, 2015.
Artigo em Chinês | WPRIM | ID: wpr-481333

RESUMO

Objective_To investigate the effects of hypoxia-inducible factor-1 alpha ( HIF-1α) inhibitor YC-1 on hy-poxia induced human pulmonary artery smooth muscle cells ( HPASMCs) proliferation, apoptosis and the expression of P53, and to explore the molecular mechanism in the processes.Methods_HPASMCs were cultured in DMEM me-dium supplemented with 10%FBS in vitro.Then divided them into four groups:normoxia, hypoxia and hypoxia+YC-1(0.01 and 0.05 mmol/L).Cell proliferation was measured by CCK-8 and apoptosis was detected by flow cytom-etry.The expressions of HIF-1αand P53 were tested by Western blot, and the mRNA expression of P53 was tested by RT-PCR.Results_Hypoxia can promote the proliferation of HPASMCs.Treatment of HPASMCs with different concentrations of YC-1 intervention for 24h obviously dropped proliferation rate (P<0.05), and the apoptosis rate increased significantly (P<0.05).YC-1 can also down-regulate the expression of HIF-1αand up-regulate the ex-pression of P53 significantly ( P<0.05 ) .Conclusions_YC-1 can inhibit hypoxia-induced HPASMCs proliferation and promote apoptosis, the mechanism is potentially related to the up-regulation of P53 expression.

19.
Journal of Medical Research ; (12): 151-154, 2015.
Artigo em Chinês | WPRIM | ID: wpr-481270

RESUMO

Objective To investigate the effects of the 2,3,4′,5-Tetrahydroxystilbene -2-O-beta-D-glucoside on the prolif-eration of PASMCs induced by hypoxia , in orde to search new drugs for the treatment and prevention of hypoxic pulmonary vascular remod -eling.Methods 3%O2 hypoxia was used to induced the proliferation of PASMCs .After hypoxic and TSG treatment for 24h, cell growth was determined by cell counting kit -8 ( CCK-8 ) , cell cycle was analysed by flow cytometry , the mRNA expression of HIF -1αwas measured by quantitative real -time PCR, and the reactive oxygen species ( ROS) production was determined by the fluorescence micro-plate reader .Results TSG can block the proliferation of PASMCs through G 0/G1 to S phase of the cell cycle arrest without cell cytotoxic-ity.Further experiments showed that TSG blocking the proliferation of PASMCs was associated suppression the mRNA expression of HIF -1αand the production of intracellular ROS in hypoxia -stimulated-PASMCs.Conclusion TSG can inhibit the proliferation of pulmo-nary artery smooth muscle cells induced by hypoxia through suppression the mRNA expression of HIF -1αand the production of intracel-lular ROS.

20.
Journal of Medical Research ; (12): 111-113, 2015.
Artigo em Chinês | WPRIM | ID: wpr-464206

RESUMO

Objective To establish the PDGF-BB-induced proliferation of rat pulmonary artery smooth muscle cells(PASMCs), and investigate the effects of the AMPK agonist AICAR on the cell cycle of PASMCs, in order to search new drugs for prevention of pulmo-nary vascular remodeling. Methods 20ng/ml PDGF-BB was used to induced the proliferation of PASMCs, and the effect of 0. 5mmol/L AICAR on the proliferation of PASMCs was observed. Western blot was used to detect the total and phosphorylated AMPK. The prolifer-ation of PASMCs was determined by CCK-8. The mRNA expression of cyclinD1, cyclinE and CDK2/4/6 were detected by flow cytometry analysis cell cycle,quantitative real-time PCR. Results Western blot Results indicated AICAR could promote the activation of AMPK. CCK-8 test Results showed that AICAR blocked the proliferation of PASMCs induced by PDGF-BB. Flow cytometry analysis indicated that AICAR arrested the cell cycle in G0/G1 to S phase. RT-PCR Results demonstrated that AICAR inhibited the mRNA expression of cy-clinD1, cyclinE and CDK2/4/6. Conclusion The AMPK agonist AICAR can block the proliferation of PASMCs induced through arrest cell cycle in G0/G1-S phase by regulation the mRNA expression of cyclin D1, cyclinE, CDK2/4/6, and AICAR has a potential applica-tion in preventing pulmonary vascular remodeling.

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