BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2018
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IF 2.559
Qing Shu,Song Lai,Xiao-Mei Wang,Yun-Long Zhang,Xiao-Lei Yang,Hai-Lian Bi,Hui-Hua Li
Pathological cardiac hypertrophy is the main risk factor for heart diseases. The ubiquitin-proteasome system (UPS) is the major intracellular protein degradation system involved in the development of cardiac hypertrophic remodeling. Ubiquitin-activating enzyme E1, a key component of the UPS, catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation via proteasome . However, the functional role of E1 (UBA1) in regulation of hypertrophic remodeling in angiotensin II (Ang II)-infused mice remains unknown. In this study, male wild-type mice were treated with UBA1 inhibitor PYR-41 at two doses of 5 and 10 mg and infused with Ang II (1000 ng/kg/min) for 14 days. Systolic blood pressure was detected by using tail-cuff system. Cardiac function was assessed by echocardiography. Hypertrophic remodeling was analyzed examined by histological examinations. The expressions of genes and proteins were detected by quantitative real-time PCR and immunoblotting analysis. After 14 days, Ang II infusion significantly increased UBA1 expression at both mRNA and protein levels in the hearts. Furthermore, Ang II-infused mice showed a significant increase in systolic blood pressure compensatory cardiac function, hypertrophy, interstitial fibrosis, inflammation and oxidative stress compared with saline-treated controls, whereas these effects were dose-dependently attenuated in PYR-41-treated mice. These beneficial actions were associated mainly with inhibition of PTEN degradation and multiple downstream mediators (AKT, ERK1/2, STAT3 , TGF-β/Smad2/3 and NF-kB(p65)). In conclusion, these results indicate that inhibition of UBA1 suppresses Ang II-induced hypertrophic remodeling, and suggest that administration of low dose PYR-41 may be a new potential therapeutic approach for treating hypertensive heart diseases.
研究领域:
心脏病学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2022
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IF 18.962
Di Sun,Han Wang,Jie Liu,Xinlian Wang,Hongbo Guo,Lijuan Xue,Libing Li,Jubo Li,Baojie Zhang,Yueguang Xue,Shilin Li,Ying Liu
Uncontrollable bleeding is the main cause of death during surgical trauma and accidental injuries. To halt the bleeding caused by arterial rupture is still challenging due to the high pressure and velocity of arterial blood flow . Enzyme-responsive hydrogels have emerged as promising solutions for hemostasis after arterial rupture, largely due to their high hemostatic efficiency and specificity. However, the existing enzyme-responsive hydrogels suffer from weak cross-linking. Here, we report the design of a hemostatic material with nanoporous , combining a transglutaminase enzyme reaction and Schiff base reaction, for percutaneous injection. Here, we show that the resulting burst pressure of the hemostatic material was 134 ± 10 mmHg, which is significantly greater than the normal systolic blood pressure . Most importantly, the material was able to efficiently stop the bleeding a pig and rat arterial vessel models, with a ~10 s gelling time and without the need for the hemostatic clamps on both ends of the vessel injury. Furthermore, the hemostatic material functioned as an anti-adhesion barrier in a rat liver model. The present study describes an effective, injectable hydrogel solution for the rapid and minimally invasive hemostatic treatment of bleeding diseases in parenchymal organs.
研究领域:
生物医学工程
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材料科学
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外科研究
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止血
✓ 已验证
产品关联
DOI
高影响因子
LUNG
·
2022
·Vol. 200
·期 5
·619-631
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IF 3.777
Zhai Cui,Zhang Nana,Wang Jian,Cao Meng,Luan Jing,Liu Huan,zhang Qianqian,Zhu Yanting,Xue Yuxin,Li Shaojun
Purpose It has been shown that activation of autophagy promotes the development of pulmonary arterial hypertension (PAH). Meanwhile, forkhead box M1 (FOXM1) has been found to induce autophagy in several types of cancer. However, it is still unclear whether FOXM1 mediates autophagy activation in PAH, and detailed mechanisms responsible for these processes are indefinite. Method PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) to rats. The right ventricle systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), percentage of medial wall thickness (%MT), α-smooth muscle actin (α-SMA) staining, and Ki67 staining were performed to evaluate the development of PAH. The protein levels of FOXM1, phospho-focal adhesion kinase (p-FAK), FAK, and LC3B were determined by immunoblotting or immunohistochemistry. Results FOXM1 protein level and FAK activity were significantly increased in MCT-induced PAH rats, this was accompanied with the activation of autophagy. Pharmacological inhibition of FOXM1 or FAK suppressed MCT-induced autophagy activation, decreased RVSP, RVHI and %MT in MCT-induced PAH rats, and inhibited the proliferation of pulmonary arterial smooth muscle cells and pulmonary vessel muscularization in MCT-induced PAH rats. Conclusion FOXM1 promotes the development of PAH by inducing FAK phosphorylation and subsequent activation of autophagy in MCT-treated rats.
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Dingyou Wang,Yuke Ji,Rui Wang,Ke Cheng,Liang Liu,Na Wu,Qing Tang,Xu Zheng,Junxia Li,Zhilong Zhu,Qinghua Wang,Xueyan Zhang,Runbo Li,Jinjin Pan,Zheng Sui,Yuhui Yuan
Hypoxic pulmonary hypertension (HPH) is a progressive cardiopulmonary system disease characterized by pulmonary vascular remodeling. Its occurrence and progression are closely related to oxidative stress. Lycopene, extracted from red vegetables and fruits, exhibits a particularly high antioxidant capacity that is beneficial for cardiovascular diseases. Nevertheless, the role and mechanism of lycopene in HPH remain unknown. Here, we found that lycopene reversed the elevated right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling induced by hypoxia in rats. In vitro, lycopene caused lower proliferation and migration of PASMCs, with higher apoptosis. Consistent with the antiproliferative result of lycopene on hypoxic PASMCs, the hippo signaling pathway associated with cell growth was activated. Furthermore, lycopene reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) activity in the lungs and serum of rats under hypoxia conditions. The expression of NOX4 in the lungs was also significantly decreased. Hypoxic PASMCs subjected to lycopene showed decreased reactive oxygen species (ROS) production and NOX4 expression. Importantly, lycopene repressed HIF-1α expression both in the lungs and PASMCs in response to hypoxia in the absence of a significant change of HIF-1α mRNA. Compared with 2ME2 (a HIF-1α inhibitor) alone treatment, lycopene treatment did not significantly change PASMC proliferation, NOX4 expression, and ROS production after 2ME2 blocked HIF-1α, suggesting the inhibitory effect of lycopene on HIF-1α-NOX4-ROS axis and the targeted effect on HIF-1α. After CHX blocked protein synthesis, lycopene promoted the protein degradation of HIF-1α. MG-132, a proteasome inhibitor, notably reversed the decrease in HIF-1α protein level induced by lycopene in response to hypoxia. Therefore, lycopene suppressed hypoxia-induced oxidative stress through HIF-1α-NOX4-ROS axis, thereby alleviating HPH. Our findings will provide a new research direction for clinical HPH therapies.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Siyi Song,Shuqi He,Qianxia Lin,Huoxi Jin
Hypertension significantly contributes to adverse cardiovascular outcomes. Our investigation was designed to evaluate the effects of supplementation with collagen peptide (LR-7) and taurine (Tau) on cardiovascular impairment in hypertensive mice induced by an 8% high-salt (HS) diet. Compared to administration of LR-7 (200 μmol/kg) or Tau (200 μmol/kg) alone, the combined treatment of LR-7 (100 μmol/kg) and Tau (100 μmol/kg) exhibited the strongest inhibition of systolic blood pressure elevation, aortic intimal thickening, reduction in myocardial fiber density, and myocardial fibrosis in HS-induced hypertensive mice. Furthermore, the treatment with LR-7+Tau significantly ameliorated the levels of cardiac adhesion factor (intercellular adhesion molecule 1), antioxidant enzymes (catalase and glutathione peroxidase), and inflammatory markers (interleukin-6, interleukin-1β, and nuclear factor kappa-B) in hypertensive mice compared to either LR-7 or Tau alone. To uncover the underlying mechanisms, the calpain 1/junctophilin-2 (JP2) pathway in cardiac tissue was investigated. Our findings revealed that LR-7+Tau treatment reversed the abnormal expression of calpain 1 and JP2 proteins in cardiac tissue. Additionally, it upregulated the endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) levels in the heart. In summary, LR-7 and Tau collectively exerted a cardiovascular protective effect in HS diet-induced hypertensive mice, demonstrating synergistic efficacy.
研究领域:
心脏病学
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）