Dataset Information

Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.

ABSTRACT: Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated. In this study, human atrial fibroblasts were stimulated with Ang II in the presence or absence of DS-201. Then, ?-smooth muscle actin (?-SMA), collagen I, and collagen III expression and reactive oxygen species (ROS) generation were measured. The expression of transforming growth factor-?1 (TGF-?1) and the downstream signaling of TGF-?1, such as phosphorylation of Smad2/3, were also determined. The results demonstrated that DS-201 significantly prevented Ang II-induced human atrial fibroblast migration and decreased Ang II-induced ?-SMA, collagen I, and collagen III expression. Furthermore, increased production of ROS and expression of TGF-?1 stimulated by Ang II were also significantly inhibited by DS-201. Consistent with these results, DS-201 significantly inhibited Ang II-evoked Smad2/3 phosphorylation and periostin expression. These results and the experiments involving N-acetyl cysteine (antioxidant) and an anti-TGF-?1 antibody suggest that DS-201 prevent Ang II-induced differentiation of atrial fibroblasts to myofibroblasts, at least in part, through suppressing oxidative stress and inhibiting the activation of TGF-?1 signaling pathway. All of these data indicate the potential utility of DS-201 for the treatment of cardiac fibrosis.

SUBMITTER: Chen T

PROVIDER: S-EPMC6081515 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.

Chen Tangting T Li Miaoling M Fan Xuehui X Cheng Jun J Wang Liqun L

Oxidative medicine and cellular longevity 20180724

Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated. In this study, human atrial fibroblasts were stimulated with Ang II in the presence or absence ...[more]

PMID: 30140368

Similar Datasets

Project description:Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy. Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy. Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. All studies were screened by two reviewers according to the inclusion and exclusion criteria independently. The Cochrane Collaboration's risk tool was used to assess the methodological quality of the included studies. Reviewer Manager 5.3 was employed for statistical analysis. Results: Sixteen trials involving 1,696 patients were included. The meta-analysis results indicated a combination of STS and angiotensin receptor blockers (ARBs) was more effective than ARB monotherapy in modulating hypertensive nephropathy, as represented by improved estimated glomerular filtration rate (eGFR) [mean difference (MD) = 6.87, 95% CI (4.47, 9.28), P < 0.00001] and reduced 24 h urinary protein [MD = -0.23, 95% CI (-0.27, -0.19), P < 0.00001], serum creatinine (SCr) [MD = -21.74, 95% CI (-24.11, -19.38), P < 0.00001], cystatin-C [MD = -0.16, 95% CI (-0.24, -0.07), P = 0.0003], urinary immunoglobulin G (IgG) [MD = -0.85, 95% CI (-1.11, -0.59), P < 0.00001], and urinary transferrin [MD = -0.61, 95% CI (-1.04, -0.17), P = 0.007]. In addition, the combination therapy had better control in systolic blood pressure (SBP) [MD = -6.53, 95% CI (-8.19, -4.87), P < 0.00001] and diastolic blood pressure (DBP) [MD = -4.14, 95% CI (-5.69, -2.59), P < 0.00001]. Only three trials reported adverse events, and no adverse drug reactions were observed. Conclusions: STS combined with ARBs had a stronger effect on improving renal function in patients with primary hypertensive nephropathy than ARB monotherapy. The combination therapy also provided auxiliary hypotensive effects. Further large-scale, multicenter, and rigorously designed randomized controlled trials (RCTs) should be conducted to confirm our findings.

Project description:Hemorrhage stroke is a severe vascular disease of the brain with a high mortality rate in humans. Salvia miltiorrhiza Bunge (Danshen) is a well-known Chinese Materia Medica for treating cerebral vascular and cardiovascular diseases in traditional Chinese medicine. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, which is the main active ingredient of Danshen. In our previous study, we established a zebrafish model of cerebral hemorrhage and found that STS dramatically decreased both the hemorrhage rate and hemorrhage area, although the underlying mechanism was not fully elucidated. We conducted a transcriptome analysis of the protective effect of STS against atorvastatin (Ator)-induced cerebral hemorrhage in zebrafish using RNA-seq technology. RNA-seq revealed 207 DEGs between the Ator-treated group and control group; the expression levels of 53 DEGs between the Ator-treated group and control group were reversed between the STS + Ator-treated group and Ator-treated group. GO enrichment analysis indicated that these 53 DEGs encode proteins with roles in hemoglobin complexes, oxygen carrier activity and oxygen binding, etc. KEGG analysis suggested that these 53 DEGs were most enriched in three items, namely, porphyrin and chlorophyll metabolism, ferroptosis, and the HIF-1 signaling pathway. The PPI network analysis identified 12 hub genes, and we further verified that Ator elevated the mRNA expression levels of hemoglobin (hbae1.3, hbae3, hbae5, hbbe2, and hbbe3), carbonic anhydrase (cahz), HIF-1 (hif1al2) and Na+/H+ exchanger (slc4a1a and slc9a1) genes, while STS significantly suppressed these genes. In addition, we found that pharmacological inhibition of PI3K/Akt, MAPKs, and mTOR signaling pathways by specific inhibitors partially attenuated the protective effect of STS against Ator-induced cerebral hemorrhage in zebrafish, regardless of mTOR inhibition. We concluded that hemoglobin, carbonic anhydrase, Na+/H+ exchanger and HIF-1 genes might be potential biomarkers of Ator-induced cerebral hemorrhage in zebrafish, as well as pharmacological targets of STS. Moreover, HIF-1 and its regulators, i.e., the PI3K/Akt and MAPK signaling pathways, were involved in the protective effect of STS against Ator-induced cerebral hemorrhage. This study also provided evidence of biomarkers involved in hemorrhage stroke and improved understanding of the effects of HMG-COA reductase inhibition on vascular permeability and cerebral hemorrhage.

Project description:AimsSodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study.MethodsRandomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed.Results19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001).ConclusionSTS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.

Dataset Information

Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.

Publications

Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets