The level of ROCK1 and ROCK2 in patients with pulmonary hypertension in plateau area

Liu, Bing; Chang, Rong; Duan, Zhili; Zhang, Xiaofei; Shen, Ying; Liu, Xiangbo; Wu, Jinchun; Tuo, Yajun; Luo, Jun

doi:10.1038/s41598-018-27321-4

Cited by 11 publications

(4 citation statements)

References 28 publications

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“…Two homologous isomers of ROCK exist: ROCK1 and ROCK2 ( Wang et al, 2019 ). The research showed that the activity of ROCK increases in patients with PAH, heart failure, hypertension, and stable angina pectoris ( Liu et al, 2018 ). ROCK is also implicated in the progression of various diseases such as HPH.…”

Section: Discussionmentioning

confidence: 99%

Tsantan Sumtang Restored Right Ventricular Function in Chronic Hypoxia-Induced Pulmonary Hypertension Rats

Yang

Sun

Su³

et al. 2021

Front. Pharmacol.

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Background: Tsantan Sumtang originated from Four Tantras, which consisted of Choerospondias axillaris (Roxb.) B. L. Burtt and A. W. Hill, Santalum album L., and Myristica fragrans Houtt. The three herbs are in ratio 1:1:1. This medication is widely used for cardiovascular diseases.Aims: The purpose of this study was to explore the effect of Tsantan Sumtang on right ventricular (RV) function in hypoxia-induced pulmonary hypertension (HPH) rats and investigate the underlying mechanism.Methods: Sixty male Sprague-Dawley (SD) rats were divided into control, hypoxia, and hypoxia + Tsantan Sumtang (1.0, 1.25, and 1.5 g•kg−1•d−1) groups. Chronic hypoxia was induced by putting the rats inside a hypobaric chamber for four weeks and adjusting the inner pressure and oxygen content to match an altitude of 4500 m. Echocardiography was used to assess RV function and right ventricular-pulmonary arterial (RV-PA) coupling. The physiological parameters of the animals were also evaluated. Morphological characteristics of RV were assessed by hematoxylin and eosin (H&E) staining and TEM. Masson’s trichrome staining, immunohistochemical staining, western blotting, and TUNEL assay were used to assess fibrosis and apoptosis levels. The antioxidant and anti-apoptosis properties of Tsantan Sumtang were also evaluated. The effect of Tsantan Sumtang on ROCK signaling pathway was evaluated using real-time quantitative PCR and western blotting.Results: We established an HPH rat model as indicated by the significant increases in the physiological parameters of the rats. Tsantan Sumtang showed a significant cardiac-protective function and an improved effect on RV-PA coupling. Moreover, Tsantan Sumtang treatment inhibited fibrosis and alleviated apoptosis and oxidative stress in RV. In terms of mechanism, Tsantan Sumtang reduced the expression of ROCK (ROCK1, ROCK2) in RV, inhibited cardiac remodeling-related transcription factors (NFATc3, P-STAT3), and regulated apoptosis-related proteins.Conclusion: Tsantan Sumtang was able to restore RV function, improve RV-PA coupling, recover hemodynamic and hematological indexes, and protect RV against structural maladaptive remodeling in the HPH rats. These findings demonstrated that Tsantan Sumtang protects the function of RV in HPH rats. The antioxidant and anti-apoptosis properties of Tsantan Sumtang may be responsible for inhibiting the ROCK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Tsantan Sumtang Restored Right Ventricular Function in Chronic Hypoxia-Induced Pulmonary Hypertension Rats

Yang

Sun

Su³

et al. 2021

Front. Pharmacol.

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“…Both ROCK1 and ROCK2 were expressed in early mouse embryos, and the developing heart highly expressed ROCK1, while ROCK2 was continuously expressed during cardiac development [18]. Studies have shown that ROCK genes play an important role in the regulation of apoptosis in animal disease models and various cell types [19][20][21][22][23]. In the rat model of ischemia-reperfusion injury, the expression of Ras homolog gene family, member A, and the activity of ROCK were increased.…”

Section: Discussionmentioning

confidence: 99%

“…Four hundred forty-one potential target genes were predicted by TargetScan and miRDB, as shown in Figure 5a. Through searching relative studies, it was found that ROCK2 is closely related to myocardial damage [14][15][16][17][18][19][20][21][22][23]. There are multiple potential binding sites for miR-133a-5p and the 3′UTR conserved region of ROCK2, as shown in Figure 5b.…”

Section: Prediction Of Mir-133a-5 Target Genementioning

confidence: 99%

Expression of miR-133a-5p and ROCK2 in Heart in Methamphetamine-Induced Rats and Intervention of Rhynchophylline

Zhou¹,

Lin²,

Chen³

et al. 2019

Pharmacology

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Introduction: Rhynchophylline, as a traditional Chinese medicine, was used for the treatment of drug addiction. Objective: To investigate miRNAs expression profile in the rat hearts of methamphetamine dependence and the intervention mechanisms of rhynchophylline. Materials and Methods: This study detected the expression profile of miRNAs in the methamphetamine-induced rat hearts by microarray and verified the expression of miR-133a-5P and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) protein. Results: After conditioned place preference training, methamphetamine significantly increased the time spent in the drug-paired compartment, while rhynchophylline and MK-801 could reduce the time. Cluster analysis results of miRNAs showed that compared with the control group, the expression of miR-133a-5p in methamphetamine-induced rat hearts was decreased significantly; rhynchophylline could significantly increase the expression of miR-133a-5p. The result was verified by real-time polymerase chain reaction. The results of target gene predictive software and related research showed that ROCK2 protein may be the target gene of miR-133a-5p. The immunohistochemistry results of heart tissues showed that the expression of ROCK2 protein was significantly upregulated in the methamphetamine group and downregulate in the rhynchophylline group; the difference between the MK-801 group and the methamphetamine group was not significant. The result of western blot was consistent with the immunohistochemistry. Conclusion: The active ingredient of Chinese herbal medicine rhynchophylline can effectively inhibit the formation of methamphetamine-dependent conditional place preference (CPP) effect in rats to some extent. MiR-133a-5p may participate in the cardioprotective effects of CPP rats by targeting ROCK2.

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“…The red blood cell distribution width (RDW) is a parameter that variability and heterogeneity in reflects red blood cell size [ 10 ]. RDW has been recognized as a potential independent risk factor for ischemic cerebrovascular disease.…”

Section: Introductionmentioning

confidence: 99%

High red blood cell distribution width levels could increase the risk of hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke patients

Fan

Liu

et al. 2021

Aging

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The association between the red blood cell distribution width (RDW) and hemorrhagic transformation (HT) after thrombolysis in acute ischemic stroke patients remains inconclusive. Our study aimed to assess whether high RDW levels are associated with the occurrence of HT after thrombolysis. Data were consecutively collected and retrospectively analyzed for stroke patients treated with thrombolysis between 1 January 2017 and 31 December 2019. The primary outcomes were the occurrence of HT and symptomatic HT. Among the 286 patients enrolled, 36 (12.6%) developed HT and15 (5.2%) were classified as symptomatic HT. Patients with high RDW levels were associated with a higher percentage of HT and symptomatic HT (P<0.05). The RDW levels in the HT and symptomatic HT groups were also greater compared with the no-HT group (P<0.001). Multivariable logistic regression analysis revealed that high RDW levels were independently associated with an increased risk of HT (adjusted odds ratio 2.5, 95 % CI, 1.74–3.83 P < 0.001). In conclusion, we found that high RDW levels may be an independent predictor of HT in stroke patients after thrombolysis.

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The level of ROCK1 and ROCK2 in patients with pulmonary hypertension in plateau area

Cited by 11 publications

References 28 publications

Tsantan Sumtang Restored Right Ventricular Function in Chronic Hypoxia-Induced Pulmonary Hypertension Rats

Tsantan Sumtang Restored Right Ventricular Function in Chronic Hypoxia-Induced Pulmonary Hypertension Rats

Expression of miR-133a-5p and ROCK2 in Heart in Methamphetamine-Induced Rats and Intervention of Rhynchophylline

High red blood cell distribution width levels could increase the risk of hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke patients

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