Frontiers in Pharmacology
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2022
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IF 5.988
Nana Li,Lei Dong,Yuanyuan Shen,Yongling Wang,Liansheng Chang,Hongwei Wu,Yuqiao Chang,Menghao Li,Dan Li,Zhaoyi Li,Mei He,Cheng Li,Yao Wei,Haiqin Xie,Feng Wang
In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W 1 /O/W 2 ) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.
研究领域:
心脏病学
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药学
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
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2023
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IF 3.4
Wang Li,Wang Chuanhe,Sun Zhaoqing,Du Aolin,Shan Fei,Sun Zhijun
Myocardial ischemia/reperfusion (MI/R) injury induces myocardial damage and dysfunction. Increasing evidence has confirmed that circular RNAs (circRNAs) play crucial roles in regulating MI/R. Mmu-circ-0001380 has identified to be highly expressed in myocardium of MI/R mouse model. However, its biological function and molecular mechanism in MI/R injury are still unclear. Here, we demonstrated that knockdown of cric-0001380 attenuated myocardial injury of MI/R mice. In vitro , silence of circ-0001380 significantly enhanced viability, and inhibited apoptosis and oxidative stress in HL-1 cells under oxygen–glucose deprivation/reoxygenation (OGD/R). Mmu-miR-106b-5p interacted with circ-0001380, and suppressed the expression of pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (Phlpp2). The miR-106b-5p/Phlpp2 axis mediated the effect of circ-0001380 on OGD/R-induced apoptosis through regulating the phosphorylation of p38, and further involved in regulating the viability and oxidative stress of HL-1 cells. In conclusion, circ-0001380 downregulation relieves MI/R injury via regulating the miR-106b-5p/Phlpp2 axis. Graphical Abstract The present study indicates that mmu-circ-0001380 exacerbates the myocardial ischemia/reperfusion injury through modulating the miR-106b-5p/Phlpp2 axis in vitro and in vivo .
研究领域:
心脏病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xiaowei Niu,Jing Zhang,Jingjing Zhang,Lu Bai,Shuwen Hu,Zheng Zhang,Ming Bai
Myocardial ischemia/reperfusion (MI/R) injury, a major contributor to poor prognosis in patients with acute myocardial infarction, currently lacks effective therapeutic strategies in clinical practice. The long noncoding RNA (lncRNA) Oip5-as1 can regulate various cellular processes, such as cell proliferation, differentiation, and survival. Oip5-as1 may have potential as a therapeutic target for MI/R injury as its upregulated expression has been associated with reduced infarct size and improved cardiac function in animal models, although how to effectively and safely overexpress Oip5-as1 in vivo remains unclear. Lipid nanoparticles (LNPs) are a versatile technology for targeted drug delivery in numerous therapeutic applications. Herein, we aimed to assess the therapeutic efficacy and safety of LNPs coloaded with Oip5-as1 and a cardiomyocyte-specific binding peptide (LNP@Oip5-as1@CMP) in a murine model of MI/R injury. To achieve this, LNP@Oip5-as1@CMP was synthesized via ethanol injection method. The structural components of LNP@Oip5-as1@CMP were physicochemically analyzed. A hypoxia/reoxygenation (H/R) model in HL-1 cells and coronary artery ligation in mice were used to simulate MI/R injury. Our results demonstrated that LNPs designed for cardiomyocyte targeting and efficient Oip5-as1 delivery were successfully synthesized. In HL-1 cells, LNP@Oip5-as1@CMP treatment significantly reduced mitochondrial apoptosis caused by H/R injury. In the murine MI/R model, the intravenous administration of LNP@Oip5-as1@CMP significantly decreased myocardial infarct size and improved cardiac function. Mechanistic investigations revealed that Oip5-as1 delivery inhibited the p53 signaling pathway. However, the cardioprotective effects of Oip5-as1 were abrogated by administrating Nutlin-3a, a p53 activator. Furthermore, no signs of major organ damage were detected after LNP@Oip5-as1@CMP injection. Our study reveals the therapeutic potential of LNPs for targeted Oip5-as1 delivery in mitigating MI/R injury. These findings pave the way for advanced targeted treatments in cardiovascular diseases, emphasizing the promise of lncRNA-based therapies.
研究领域:
心血管疾病
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纳米技术
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2022
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IF 6.656
Linhao Xu,Daqiang He,Yirong Wu,Lishui Shen,Yongmei Wang,Yizhou Xu
Background Heart failure (HF) is a common cardiovascular syndrome. Tanshinone IIA (Tan IIA) is a pharmacologically active monomer that exerts a significant cardioprotective effect in the clinic; however, the specific mechanisms are not fully understood. Purpose We mainly investigated the protective effects of Tan IIA on doxorubicin (DOX)-induced HF. Methods In an in vitro study, H9C2 and HL-1 cells were cultured and treated with DOX and Tan IIA for 24 h, we investigated the mechanism underlying Tan IIA-mediated protection. In an in vivo study, a model of DOX-induced HF was established in C57BL/6 mice that were divided into the six groups randomly: a control group, a DOX group, DOX groups treated with Tan IIA (DOX+Tan IIA) at dosages of 2.5, 5 and 10 mg/kg/day and DOX groups treated with N-acetylcysteine (NAC) at dosages of 200 mg/kg/day. Result The results demonstrated that Tan IIA significantly increased cell viability and protected against DOX-induced apoptosis. RNA-sequencing showed that the genes expression associated with the apoptotic signaling pathway was altered by Tan IIA. Among the differentially expressed genes, death-domain associated protein (DAXX), which plays an critical role in apoptotic signaling, exhibited increased expression under Tan IIA treatment. In addition, RNA interference was used to silence the expression of DAXX, which abolished Tan IIA-mediated protection against DOX-induced apoptosis; this effect was associated with extracellular signal-regulated protein kinase 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) expression. In the in vivo study, the echocardiography results revealed that heart function was rescued by Tan IIA, and the histomorphology results showed that Tan IIA prevented myocardial structural alteration and myofibril disruption. Furthermore, Tan IIA induced the expressions of DAXX, p-ERK1/2 and p-MEK. Tan IIA also inhibited apoptosis by suppressing the expression of cleaved caspase-8, p-P38 and cleaved caspase-3. Conclusion Our results provide novel interpretations into the important role of DAXX in DOX-induced cardiotoxicity and show that Tan IIA may be a novel agent strategy for HF treatment via activating the DAXX/MEK/ERK1/2 pathway.
研究领域:
心脏病学
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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
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2023
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IF 11.2
E Zhang,Chuangeng Shang,Mingtao Ma,Xuanfeng Zhang,Yu Liu,Shuliang Song,Xia Li
Polyguluronic acid (PG), a polysaccharide from alginate , possesses excellent bioactivities. We prepared high-purity PG with 10.41 kDa molecular weight (Mw) and a 59 average degree of polymerization (DP) by acid hydrolysis , three pH grades, Q-Sepharose column elution, and Sephadex G-25 column desalination . Then, we evaluated the PG protective effects on doxorubicin-induced cardiotoxicity (DIC) in vitro and in vivo. The nontoxic PG enhanced cellular viability , reduced cell pyroptosis morphology, diminished the LDH and IL-1β release, and downregulated expressions of ASC oligomerization , NLRP3 , cl-CASP1, and GSDMD, by which PG protected the cardiomyocytes from NLRP3 inflammasome-mediated pyroptosis in doxorubicin-stimulated HL-1 cells and C57BL/6J mice. The probable underlying mechanism may be that PG downregulated doxorubicin -induced Peli1, the deficiency of which could inhibit doxorubicin-induced NLRP3 inflammasome-mediated pyroptosis. These results suggested that polysaccharide PG from alginate could prevent DIC and may be a potential therapeutic agent or bioactive material for preventing DIC.
研究领域:
药理学
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心脏病学
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免疫学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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