BMC Pulmonary Medicine
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2025
·Vol. 25
·期 1
·1-13
·
IF 2.8
Huang Zhiheng,Li Liangxian,Zhang Bingxi,Yao Dong,Xiao Bo,Mo Biwen
Background Bronchial asthma, a chronic inflammatory airway disease, is characterized by airway remodeling, including thickening of the airway smooth muscle layer, primarily due to abnormal proliferation of airway smooth muscle cells (ASMCs). CBL0137 (Curaxin-137 hydrochloride), a histone chaperone facilitate chromatin transcription (FACT) inhibitor, has demonstrated anti-tumor properties, including inhibition of proliferation, promotion of apoptosis, and increased autophagy. However, its effects on ASMCs and airway remodeling remain unexplored. Methods Asthma models were established using ovalbumin (OVA) in female C57BL/6 J mice, with therapeutic interventions using CBL0137 and budesonide. Lung tissues were analyzed using Hematoxylin and eosin (H&E), PAS, Masson’s trichrome, and α-SMA immunofluorescence staining. ASMCs extracted from Sprague–Dawley rats were cultured in vitro experiments, with phenotypic changes assessed via flow cytometry. Gene and protein expressions were analyzed using RT-PCR and Western blotting. Results CBL0137 significantly reduced airway resistance, goblet cell proliferation, alveolar collagen deposition, and airway smooth muscle layer thickening in asthmatic mice. In vitro, CBL0137 inhibited ASMC proliferation and induced apoptosis, downregulating cyclin-B1, Cdc2, and Bcl-2 while upregulating caspase-3. Conclusions CBL0137 mitigates airway remodeling of asthmatic mice by modulating ASMC proliferation and apoptosis, presenting a potential therapeutic strategy for asthma treatment.
研究领域:
药理学
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呼吸病学
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分子生物学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2015
·Vol. 12
·期 5
·6656-6662
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IF 1.554
Chengfei Zheng,Hui Niu,Ming Li,Hongkun Zhang,Zhenggang Yang,Lu Tian,Ziheng Wu,Donglin Li,Xudong Chen
Aortic aneurysm is a cardiovascular condition with a serious risk of mortality and the dismal prognosis of any type of major cardiovascular disease. The present study found that tissues from aortic aneurysm patients and hypoxic aortic smooth muscle cells showed aberrant high expression of the cyclic RNA hsa‑circ‑000595, as demonstrated by polymerase chain reaction array screening. Knockdown of hsa‑circ‑000595 resulted in a decreased apoptotic rate of human aortic smooth muscle cells. Furthermore, it was determined that miR‑19a is a target of hsa‑circ‑000595. The results of the present study laid an epigenetic foundation for exploring the underlying mechanisms of the development of aortic aneurysm.
研究领域:
心血管疾病
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
·
IF 5.6
Yu Shi,Yi Zhao,Si-Jia Sun,Xiu-Ting Lan,Wen-Bin Wu,Zhen Zhang,Yu-Xin Chen,Yu-Ying Yan,Yu-Ping Xu,Dong-Jie Li,Hui Fu,Fu-Ming Shen
Abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease, closely related to inflammation and loss of vascular smooth muscle cells (VSMCs). Ferroptosis is an iron-dependent cell death associated with peroxidation of lipids. However, the direct role of glutathione peroxidase 4 (GPX4) itself determined ferroptosis in the course of AAA pathogenesis remains unknown. Here, we reported that ferroptosis was triggered in human AAA, elastase- and angiotensin II (Ang II)-induced mouse AAA, and Ang II-incubated VSMCs. Inhibition of ferroptosis via global genetic overexpression of GPX4, a critical anti-ferroptosis molecule, markedly prevented both vascular remodeling and inflammatory response. Mechanistically, GPX4 changed the migration and activation of macrophages/monocytes in AAA tissues in mice. Experiments in vitro demonstrated that overexpression of GPX4 prevented the JAK1/STAT3 signaling activation in VSMCs induced by IL-6, production of pro-inflammatory macrophages. Finally, the role of ferroptosis was confirmed on an Ang II-induced mice AAA model. These results emphasized the significance of ferroptosis in AAA, and provided novel insights that therapy focusing on GPX4 might be a promising strategy for treatment of AAA in the clinic.
研究领域:
心血管疾病
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
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2025
·
IF 4.2
Wen Xin,Peng Yuefeng,Yang Wenqing,Zhu Yuzhong,Yu Fan,Geng Li,Wang Xianfeng,Wang Xiaoyan,Zhang Xiaodong,Tang Yi,Feng Lei,Zhou Tingting,Jia Hongliang,Yang Liu
Transient receptor potential canonical 1 (TRPC1) channel, a Ca 2+ -permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. Key messages
AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice.
TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling.
Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.
研究领域:
心血管病学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Jiayi Zhang,Yang Li,Zhen Xiang,Hongxia Pu,Cheng Ji,Xingrong Ren,Daihua Fu,Yunbing Wang
Stent implantation remains a cornerstone of interventional cardiology, providing a minimally invasive solution to restore blood flow in occluded vessels. However, current stents face persistent challenges in simultaneously preventing neointimal hyperplasia and promoting reendothelialization, compromising their long-term efficacy. To address these limitations, we developed an in situ H2S-releasing polymer brush-coated stent that actively modulates material–blood interactions, creating a favorable microenvironment for vascular healing. H2S enhances the stent’s antithrombotic properties by inhibiting fibrinogen binding and platelet activation, while also mitigating oxidative stress and promoting macrophage polarization toward the anti-inflammatory M2 phenotype. In vivo, the H2S-releasing stents significantly improved vascular healing by accelerating endothelialization and inhibiting smooth muscle cell overproliferation, resulting in a thinner neointima with functional endothelial coverage. Transcriptomic analysis further elucidated the underlying mechanisms, revealing H2S-mediated modulation of key biological pathways that support vascular healing. These findings underscore the potential of in situ H2S release as an effective strategy for optimizing vascular implants and improving long-term outcomes.
研究领域:
心血管医学
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生物材料学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Gastroenterology Research and Practice
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2020
·
IF 1.806
Guo-xiang Wang,Yan-li Xiang,Hong-gang Wang,Yang-de Miu,Guang Yu
Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 μM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents () in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I–V) relationship of L-type calcium channels was modified by Evo, while the peak of the I–V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak . The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.
研究领域:
药理学
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生理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Feng Jia,Yongqing Wang,Zhiqiang Chen,Jingxian Jin,Lei Zeng,Li Zhang,Huaijian Tang,Yanyan Wang,Pei Fan
Background 10-Hydroxydec-2-enoic acid (10-HDA), a unique and marker compound in royal jelly, has a wide range of bio-activities. However, its role in regulating inflammation of vascular smooth muscle cell (VSMC), which is essential to a set of vascular diseases, is still unknown. Purpose Our study aimed to investigate whether 10-HDA exerts effect on VSMC inflammation via interacting with toll-like receptor 4 (TLR4), a pivotal inflammatory initiator. Methods A package of proteins, which might participate in TLR4-mediated signaling, influenced by 10-HDA were analyzed in mouse VSMCs with Angiotensin Ⅱ(Ang Ⅱ) or lipopolysaccharide (LPS) stimulation. Accordingly, pro- or anti-inflammatory cytokines, reactive oxygen species (ROS), and anti-oxidants that are closely relevant to inflammatory process were determined. The possible mode for 10-HDA interacting with TLR4 was also characterized. Moreover, involvement of a key miRNA in 10-HDA regulating VSMC inflammation was identified. Results In the presence of Ang Ⅱ, 10-HDA inhibited the TLR4 expression in a dose-dependent manner. In such occasion, 10-HDA hindered the up-regulation of specificity protein 1 (SP1) and serine/threonine-protein phosphatase 6 catalytic subunit (PPP6C), the phosphorylation of extracellular signal-regulated kinase 1/2, TGF-β-activated kinase 1, and nuclear factor-κB p56, as well as the enhancement of myeloid differentiation primary response gene 88. Apart from SP1 and PPP6C, the level change of these proteins by 10-HDA was similar with LPS stimulation. The effect might be resulted from 10-HDA blocking TLR4 through multiple atomic interactions. 10-HDA mitigated the increase of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-2 (IL-2), and IL-6, as well as increased the anti-inflammatory cytokine IL-10, in the Ang Ⅱ- or LPS-induced VSMCs. Correspondingly, the level of ROS was attenuated and the anti-oxidants such as glutathione and superoxide dismutase were fortified. The data indicated the anti-inflammatory potential of 10-HDA in VSMCs, which was associated with 10-HDA's capability of relieving oxidative stress. Additionally, the expression of miR-17–5p was saved by 10-HDA from Ang Ⅱ- or LPS-treated VSMCs, which might be relevant to SP1 and PPP6C targeting. Conclusion The present work of 10-HDA, for the first time, revealed its ability to alleviate VSMC inflammation by targeting TLR4 and therefore modulate the downstream inflammatory participants. Our data will cast light on the utilization of 10-HDA in VSMC inflammation-related vascular disorders.
研究领域:
药理学
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分子生物学
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心血管疾病
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DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
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2022
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IF 7.31
Lili Shi,Yuliang Li,Meixin Shi,Xiaoxue Li,Guopeng Li,Jie Cen,Dan Liu,Can Wei,Yan Lin
Background. It is well-known that dysfunctions of vascular smooth muscle cells (VSMCs) act an essential part in vascular complications of diabetes. Studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) play a crucial role in regulating cell functions. However, their influence on the proliferation, calcification, and autophagy of VSMCs remains to be further explored. Therefore, this study elucidates the role and mechanism of hsa_circRNA_0008028 in high glucose- (HG-, 30 mM) treated VSMCs in vitro. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was chosen to detect the levels of hsa_circRNA_0008028, miR-182-5p, and tribble 3 (TRIB3). Then, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to predict and verify the binding relationship between miR-182-5p and hsa_circRNA_0008028 or TRIB3. Cell counting kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU) staining, corresponding commercial kits, and western blotting were used to measure indexes reflecting cell viability, proliferation, calcification, and autophagy of VSMCs, respectively. Results. In HG-induced VSMCs, hsa_circRNA_0008028 and TRIB3 were highly expressed, whereas miR-182-5p decreased. Meanwhile, cell proliferation, calcification, and autophagy could be repressed by silencing of hsa_circRNA_0008028. However, these effects can be eliminated by miR-182-5p inhibition. Furthermore, it was demonstrated that hsa_circRNA_0008028 could promote the expression of TRIB3, a target of miR-182-5p, by directly sponging miR-182-5p. The expression of TRIB3 was suppressed by hsa_circRNA_0008028 knockout, which was rescued by miR-182-5p inhibition. Conclusion. This study reveals that hsa_circRNA_0008028 can act as a sponge of miR-182-5p and promote HG-induced proliferation, calcification, and autophagy of VSMCs partly by regulating TRIB3.
研究领域:
分子生物学
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细胞生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
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IF 14.1
Yanjun Liu,Jianxujie Zheng,Lingyan Zhong,Zengyu Wang,Dan Zhao,Hong Lin,Xiaoxue Zhang,Ke Meng,Xiaoxia Yang,Dongxue Zhang,Ling Lin,Liang Qiao
Hypertension, the leading cause of cardiovascular disease and premature mortality, is characterized by increased vessel stretch and alterations in vascular smooth muscle cells (VSMCs). In this study, a vessel-on-a-chip model is developed to simulate both physiological and pathological stretch conditions alongside a mouse model of hypertension. Proteomics analysis is applied to investigate changes in VSMCs using the vessel-on-a-chip system and compared these findings with data from the mouse model. The results demonstrates that physiological stretch enhances the expression of contractile markers in VSMCs. Additionally, the chip effectively replicates cellular responses to pathological stretch and stress, including the upregulation of ERK signaling, calcium ion transport pathway, integrin signaling pathway, endoplasmic reticulum stress, toll-like receptor activation, oxidative stress, and synthesis of sphingolipids and ceramides. These findings indicate that the vessel chip successfully mimics in vivo biological events associated with hypertension. The vessel-on-a-chip system holds promise for advancing the study of vessel-related diseases and facilitating the development of novel hypertension therapeutics.
研究领域:
生物医学工程
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心血管科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Future Science OA
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2025
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IF 2.1
Chunyang Wei,Xiaoying Liu,Zhuang Miao,Hua Zhang,Yanfu Wang,Guoxian Qi
Aim The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.Methods Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated. Additionally, the role of p38 phosphorylation pathway in the effect of TWEAK on VSMCs senescence was assessed.Results Expressions of TWEAK and Fn14 were significantly elevated in senescent VSMCs. TWEAK activated the p38 phosphorylation pathway and promoted the SA-β-gal staining and P53 expression.Conclusion These preliminary findings suggest that the TWEAK/Fn14 axis may play a crucial role in promoting VSMC senescence.
研究领域:
心血管研究
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细胞信号传导
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
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IF 4.7
Jie Yan,Xiaowen Zhang,Lifeng Feng,Shengzheng Zhang,Han Wei,Wencong Tian,Qiwen Li,Jing Li,Liang Yang,Jie Liu,Yang Xu,Jianlin Cui,Shan Ren,Zhi Qi,Yang Gao
Hypertension is a primary risk factor for cardiovascular disease. Recently, Ertugliflozin (Ertu), a new sodium-glucose cotransporter-2 (SGLT2) inhibitor, though primarily approved by the FDA as an antidiabetic agent, has been reported to lower blood pressure. However, whether Ertu directly regulates the contractility of arteries remains unknown. Here, we examined Ertu's effects on vascular function and underlying molecular mechanisms. Isometric tension of arteries was recorded using a multi-wire myograph system. In rat mesenteric arteries, Ertu acutely relaxed vessels constricted by phenylephrine (PE) and high K + (KPSS), while pretreatment with Ertu inhibited PE- and KPSS- induced vascular constriction. Similar outcomes were observed in the mouse thoracic aorta. Notably, these vasodilatory effects of Ertu are mediated by vascular smooth muscle cells (VSMCs) rather than endothelial cells. Mechanistically, we found that Ertu activated AMP-activated protein kinase (AMPK) signaling pathway in VSMCs and rat thoracic aorta tissues by decreasing ATP levels and the ATP/ADP ratio. Using the AMPK inhibitor Compound C, we observed that Ertu-induced vasodilation was abolished. Furthermore, we found that Compound C reversed Ertu-mediated reductions in cytosolic calcium concentration ([Ca 2+ ]i) and mitochondrial fission, which were accompanied by diminished mitochondrial membrane potential in VSMCs. In conclusion, this study demonstrates for the first time that Ertu inhibits AMPK-mediated mitochondrial fission in VSMCs, leading to vasorelaxation, suggesting its potential as a therapeutic agent for hypertension.
研究领域:
药理学
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心血管生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2020
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IF 8.724
Mi Hu,Fan Jia,Wei-Pin Huang,Xu Li,Deng-Feng Hu,Jing Wang,Ke-Feng Ren,Guo-Sheng Fu,Yun-Bing Wang,Jian Ji
Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis, angiosteosis, and vascular aging. Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell. Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering, regenerative medicine, and medical devices. Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells (VECs) and smooth muscle cells (VSMCs). Interestingly, our findings demonstrate that, with the increase of substrate stiffness, the autophagy level of VECs and VSMCs showed differential changes: endothelial autophagy levels reduced, leading to the reductions in a range of gene expression associated with endothelial function; while, autophagy levels of VSMCs increased, showing a transition from contractile to the synthetic phenotype. We further demonstrate that, by inhibiting cell autophagy, the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased, suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing. Although the underlying mechanism requires further study, this work highlights the relationship of substrate stiffness, autophagy, and vascular cell behaviors, and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications.
研究领域:
生物医学工程
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细胞生物学
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心血管科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）