Frontiers in Pharmacology
·
2026
·
IF 5.4
Yudan Wang,Yu Chen,Wenjuan Quan,Taoli Sun,Zhe Shi,Qinhui Tuo
BackgroundAberrant VSMC proliferation, migration, and phenotypic switching drive vascular remodeling. Oxidative stress is pivotal, but effective antioxidants are limited.MethodsA catalase-loaded nanocapsule (CAT-nc) was developed for sustained ROS scavenging in Ang II-induced VSMCs.ResultsCAT-nc reduced ROS, inhibited proliferation/migration, restored contractile phenotype via PTEN reactivation and NLRP3 suppression; PTEN inhibition abolished these effects.DiscussionConfirming the ROS-PTEN-NLRP3 axis, CAT-nc attenuates oxidative stress-driven VSMC switching, offering a promising nanotherapy for vascular diseases.
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PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 9
·e70608
·
IF 4.2
Wentao Liu,Yuan Wang,Chen Liu,Bowei Shi,Xiaowei Xiong,Sheng Chen,Qianqian Huang,Li Wang,Guohua Zeng,Qiren Huang
Atherosclerosis (AS) is the primary pathological basis of many cardiovascular diseases, and the formation of foam cells plays a critical role in the progression of AS. Increasing evidence shows that a considerable proportion of foam cells derive from vascular smooth muscle cells (VSMCs) in atherosclerotic plaques. Osteopontin (OPN), a glycosylated protein secreted by cells, is supposed to promote the development of AS. However, the underlying mechanisms of OPN contributing to the AS progression remain unclear. Therefore, the purpose of the study is to investigate the effects and mechanisms of OPN on VSMC-foaming and AS. Mouse AS model was established by feeding ApoE −/− mice with high fat diet (HFD), and the foam cell model of murine aortic vascular smooth muscle cells (MOVAS) was induced with Ox-LDL. During modeling, both ApoE −/− mice and MOVAS were infected with mouse recombinant adenoviruses expressing OPN (Ad-OPN). Our results show that OPN aggravates vascular smooth muscle dysfunction and AS in the ApoE −/− mice fed with HFD. Besides, OPN reduces cholesterol efflux and further promotes the formation of VSMC-derived foam cells by decreasing the expressions of ABCA1 and ABCG1. Furthermore, OPN inhibits the phosphorylation of p38MAPK through binding to its membrane receptor CD44, thereby reducing the expressions of LXRα, ABCA1, and ABCG1. Our results demonstrate that OPN reduces the expression of cholesterol transporters ABCA1 and ABCG1 and promotes the formation of VSMC-derived foam cells, exacerbating the development of AS. The findings would provide a more powerful theoretical support for preventing and treating AS with OPN as the target. Graphical OPN binding to CD44 inhibits the phosphorylation of p38MAPK, thereby reducing the expression of downstream LXRα, ABCA1, and ABCG1, resulting in decreased cholesterol efflux and increased foaming of VSMCs, ultimately exacerbating atherosclerosis.
研究领域:
心血管疾病
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分子生物学
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PubMed
高影响因子
MATERIALS & DESIGN
·
2026
·
IF 8.2
Ying Zhang,Yadan Yang,Li Guo,Xuan Yi,Chen Huang
Vascular stent implantation is the most direct and effective approach for the treatment of atherosclerosis-related cardiovascular diseases. However, although various stents with the specific features are developed, the in-stent restenosis (ISR) still significantly impacts long-term prognosis of patients and imposes a substantial medical burden. Herein, we coated the bare metal stent (BMS) with polydopamine-Au (PDA-Au) nano-composite and then complexed with Ca 2+ , obtaining BMS@PDA-Au/Ca stent for the prevention of ISR after implantation. Under 808-nm laser irradiation, BMS@PDA-Au/Ca stent increased the temperature around it, further inducing the up-expression of transient receptor potential vanilloid subfamily 1 (TRPV1) of vascular smooth muscle cells (VSMCs). Moreover, BMS@PDA-Au/Ca stent could release Ca 2+ and Ca 2+ was promoted to enter into VSMCs through TRPV1, resulting in the enhanced contractile phenotype and decreased synthetic phenotype of VSMCs. Additionally, PDA with free radical scavenging capacity could accelerate the endothelialization repair. In this way, ISR caused by implantation of stent into the carotid arteries of rabbits could be effectively prevented by using BMS@PDA-Au/Ca stent and laser irradiation. Therefore, this study constructed a novel stent and explored its effect on prevention of ISR, providing an innovative strategy for optimizing the stent implantation treatment of atherosclerotic diseases.
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Experimental and Therapeutic Medicine
·
2024
·Vol. 28
·期 3
·1-11
·
IF 2.4
Wenxian Tu,Meina Feng,Qin Zhou,Yunfeng Wang,Mingye Wan,Danqun Gong,Jin Li,Yuanmin Du
Evidence has shown that microRNAs (miRNAs/
miRs) play key roles in biological functions of vascular smooth muscle cells (VSMCs). However, the role of miR‑374a in VSMCs remains to be elucidated. The present study aimed to explore the influence of miR‑374a on VSMCs and its molecular mechanism. The expression level of miR‑374a was measured by reverse transcription‑quantitative (RT‑q) PCR. MTT and Transwell assay were employed to assess the role of miR‑374a in proliferation and migration of VSMCs. To order to determine miR‑374a targets, a dual‑luciferase reporter assay was conducted, which was further verified by rescue experiments. Chromatin Immunoprecipitation Assay and JASPAR databases were applied to explore the regulatory association between GATA binding protein 2 (GATA2) and miR‑374a. Western blotting or RT‑qPCR were employed to detect the protein expression levels of GATA2 or RAR‑related orphan receptor A (RORA). The present study found that miR‑374a was elevated in VSMCs following treatment with platelet‑derived growth factor‑BB (PDGF‑BB) compared with that in control group. In addition, the results demonstrated that a higher expression of a miR‑374a could promote proliferation and migration of VSMCs while miR‑374a inhibitor suppressed the PDGF‑BB‑induced proliferation and migration of VSMCs in vitro. Furthermore, circTADA2A bound to miR‑374a and then upregulated RORA expression, which resulted in inhibition in VSMCs proliferation and migration. On the other hand, the result indicated that GATA2 overexpression could augment the proliferation, migration of PDGF‑bb‑induced VSMCs, which could be rescued by miR‑374a inhibitor. The findings suggested that the GATA2/circTADA2A‑miR‑374a axis promoted the proliferation and migration of VSMCs by targeting RORA, which were closely related to atherosclerosis (AS). Thus the results might offer a new therapeutic target for AS.
研究领域:
分子生物学
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心血管疾病
·
细胞生物学
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Sheng-wen Zhou,Jing Wang,Sheng-yu Chen,Ke-feng Ren,You-xiang Wang,Jian Ji
Changes in the stiffness of the cellular microenvironment are involved in many pathological processes of blood vessels. Substrate stiffness has been shown to have extensive effects on vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). However, the material stiffness of most previously reported in-vitro models is ranging from ~100 kPa to the magnitude of MPa, which does not match the mechanical properties of natural vascular tissue (10–100 kPa). Herein, we constructed hydrogel substrates with the stiffness of 18–86 kPa to explore the effect of physiological stiffness on vascular cells. Our findings show that, with the increase of stiffness at the physiological range, the cell adhesion and proliferation behaviors of VECs and VSMCs are significantly enhanced. On the soft substrate, VECs express more nitric oxide (NO), and VSMCs tend to maintain a healthy contraction phenotype. More importantly, we find that the number of differentially expressed genes in cells cultured between 18 kPa and 86 kPa substrates (560 in VECs, 243 in VSMCs) is significantly higher than that between 86 kPa and 333 kPa (137 in VECs, 172 in VSMCs), indicating that a small increase in stiffness within the physiological range have a higher impact on vascular cell behaviors. Overall, our results expanded the exploration of how stiffness affects the behavior of vascular cells at the physiological range.
研究领域:
生物医学工程
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细胞生物学
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组织工程
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高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
Yujing Wang,Min Xiao,Feng Cai,Yang Li,Tianli Shi,Xiaoyan Zhou,Shuhong Tian,Denggao Huang
Vascular calcification (VC) is a common complication of chronic kidney disease (CKD). VC is a gene-regulated process similar to osteogenic differentiation. There are still no convincing schemes to prevent and reduce the development of VC. It has been reported that hypoxia-inducing factor 1α (HIF-1α) and endothelin-1(ET-1) are related to VC. In this study, we found that the expression of ET-1 and HIF-1α was enhanced after VC, the interaction between HIF-1α and ET-1 was confirmed by CO-IP and luciferase experiments. We found that ET-1 was an upregulated differential gene of calcified vascular smooth muscle cells (VSMCs) through gene sequencing. However, hypoxia-inducing factor 2α (HIF-2α) and HIF-1α have antagonistic effects on each other. HIF-1α is a pro-inflammatory cytokine, and HIF-2α can improve inflammation and fibrosis. Roxadustat, as a selective PHD3 inhibitor, preferentially activates HIF-2α. It is still unclear whether roxadustat improves VC in CKD by regulating the expression of HIF-2α/HIF-1α. Alizarin red staining and western blot as well as immunohistochemical results showed that roxadustat could significantly reduce the degree of vascular and VSMCs calcification in CKD rats. Serum HIF-1α and ET-1 were significantly decreased after roxadustat treatment. In addition, western blot results showed that roxadustat could decrease the expression of HIF-1α and ET-1 in vascular tissues and calcified VSMC, but HIF-2α expression significantly increased. Interestingly, our study confirmed that activation of HIF-1α or inhibition of HIF-2α reversed the ameliorating effect of roxadustat on VC, proving that the effect mediated by roxadustat is HIF-2α/HIF-1α dependent. We have demonstrated for the first time that roxadustat improves VC in CKD rats by regulating HIF-2α/HIF-1α, thus providing a new idea for the application of roxadustat in VC of CKD.
研究领域:
药理学
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肾病学
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分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 23
·12888
·
IF 4.9
Ziwei Hao,Yuting Han,Qi Zhao,Minghui Zhu,Xiaoxuan Liu,Yingyu Yang,Ning An,Dinglin He,Etienne Lefai,Kenneth B. Storey,Hui Chang,Manjiang Xie
Hibernating mammals experience severe hemodynamic changes over the torpor–arousal cycle, with oxygen consumption reaching peaks during the early stage of torpor to re-enter arousal. Melatonin (MT) can improve mitochondrial function and reduce oxidative stress and inflammation. However, the regulatory mechanisms of MT action on the vascular protective function of hibernators are still unclear. Morphology, hemodynamic, mitochondrial oxidative stress, and inflammatory factors of the carotid artery were assessed in ground squirrels who were sampled during summer active (SA), late torpor (LT), and interbout arousal (IBA) conditions. Changes were assessed by methods including hematoxylin and eosin staining, color Doppler ultrasound, ELISA, Western blots, and qPCR. Changes in arterial blood and serum melatonin were also measured by blood gas analyzer and ELISA, whereas mitochondrial oxidative stress and inflammation factors of primary vascular smooth muscle cells (VSMCs) were assessed by qPCR. (1) Intima-media carotid thickness, peak systolic velocity (PSV), end diastolic blood flow velocity (EDV), maximal blood flow rate (Vmax) and pulsatility index (PI) were significantly decreased in the LT group as compared with the SA group, whereas there were no difference between the SA and IBA groups. (2) PO2, oxygen saturation, hematocrit and PCO2in the arterial blood were significantly increased, and pH was significantly decreased in the LT group as compared with the SA and IBA groups. (3) The serum melatonin concentration was significantly increased in the LT group as compared with the SA and IBA groups. (4) MT treatment significantly reduced the elevated levels of LONP1, NF-κB, NLRP3 and IL-6 mRNA expression of VSMCs under hypoxic conditions. (5) Protein expression of HSP60 and LONP1 in the carotid artery were significantly reduced in the LT and IBA groups as compared with the SA group. (6) The proinflammatory factors IL-1β, IL-6, and TNF-α were reduced in the carotid artery of the LT group as compared with the SA and IBA groups. The carotid artery experiences no oxidative stress or inflammatory response during the torpor–arousal cycle. In addition, melatonin accumulates during torpor and alleviates oxidative stress and inflammatory responses caused by hypoxia in vitro in VSMCs from ground squirrels.
研究领域:
生理学
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分子生物学
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神经科学
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心血管研究
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高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Pingli Wu,Lina Wang,Wen Li,Yu Zhang,Yifan Wu,Dengke Zhi,Hongjun Wang,Lianyong Wang,Deling Kong,Meifeng Zhu
Design and fabrication of scaffolds with three-dimensional (3D) topological cues inducing regeneration of the neo-tissue comparable to native one remains a major challenge in both scientific and clinical fields. Here, we developed a well-designed vascular graft with 3D highly interconnected and circumferentially oriented microchannels by using the sacrificial sugar microfiber leaching method. The microchannels structure was capable of promoting the migration, oriented arrangement, elongation, and the contractile phenotype expression of vascular smooth muscle cells (VSMCs) in vitro . After implantation into the rat aorta defect model, the microchannels in vascular grafts simultaneously improved the infiltration and aligned arrangement of VSMCs and the oriented deposition of extracellular matrix (ECM), as well as the recruitment and polarization of macrophages. These positive results also provided protection and support for ECs growth, and ultimately accelerated the endothelialization . Our research provides a new strategy for the fabrication of grafts with the capability of inducing arterial regeneration, which could be further extended to apply in preparing other kinds of oriented scaffolds aiming to guide oriented tissue in situ regeneration.
研究领域:
组织工程
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生物医学工程
·
再生医学
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高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 8
·3307-3319
·
IF 5.251
Bin Gao,Qiaoping Zhang,Xiaoyu Wang,Meiyu Wang,Xiang-kui Ren,Jintang Guo,Shihai Xia,Wencheng Zhang,Yakai Feng
Small interfering RNA (siRNA)-based therapy is an emerging treatment to address serious cardiovascular disease. It is essential to construct highly efficient vehicles for therapeutic siRNA intracellular delivery. Extracellular signal-regulated kinase-2 (ERK2) siRNA (abbreviated as ERK2-siRNA) is known as a type of siRNA to selectively silence the expression of ERK2. Herein, a type of ternary delivery system characterized by an endosome-selective-self-accelerating-escape ability was designed and prepared for the purpose of inhibiting the migration of vascular smooth muscle cells (VSMCs) in vitro. This system was called ternary ERK2-siRNA complexes (abbreviated as TRCs-Aco), which were fabricated via sequential electrostatic self-assembly of a star-shaped cell-penetrating peptide based on polyhedral oligomeric silsesquioxane (POSS-(C-G-R8-G-W)16), ERK2-siRNA and a pH-sensitive anionic polymer of cis-aconitic anhydride grafted ε-poly(L-lysine). Importantly, TRCs-Aco could break down the obstacle of biocompatibility-silencing efficiency. In comparison with the parent binary siRNA complexes (abbreviated as BRCs), which are composed of POSS-(C-G-R8-G-W)16 and ERK2-siRNA, our designed TRCs-Aco revealed more excellent biocompatibility including hemocompatibility and cytocompatibility. Unexpectedly, TRCs-Aco exhibited stronger ERK2 silencing efficiency at the level of mRNA and protein, which was mainly due to its remarkable self-accelerating endosomal escape. Definitive evidence demonstrated that this ternary ERK2-siRNA delivery system significantly prevented the migration of VSMCs and decreased the dermal thickness in bleomycin-treated mice. In brief, this unique structured system could provide a valuable nanoplatform for highly efficient siRNA delivery in VSMCs, and it might hold great potential in guiding ERK2-siRNA-based proliferative disease therapy.
研究领域:
纳米技术
·
药学
·
心血管疾病
·
分子生物学
·
治疗学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Yicheng Wang,Miaoyun Qiu,Bixuan Yue,Mingliang Wang,Luoxing Xia,Fengfeng Li,Chaobo Yang,Zhigao Song,Yushan Liao,Wei Liu,Zhi Zeng
Di-(2-ethylhexyl) phthalate (DEHP), a widely utilized plasticizer, has been increasingly associated with cardiovascular risks. However, the involvement of DEHP in abdominal aortic aneurysm (AAA) remains unclear. To address this gap, C57BL/6 J mice were intragastrically administered with DEHP for 4 weeks in a CaCl₂-induced AAA model. We found that DEHP exacerbated AAA progression, as evidenced by a notable enlargement in the maximal diameter of the abdominal aorta, enhanced vascular inflammation, and accelerated elastin degradation. In vitro experiments confirmed that DEHP, along with its primary metabolite mono-(2-ethylhexyl) phthalate (MEHP), induced M1 macrophage polarization, leading to increased secretion of inducible nitric oxide synthase (iNOS), matrix metalloproteinase-9 (MMP9), and pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Mechanistically, we demonstrated that DEHP and MEHP triggered the activation of the nuclear factor-kappa B (NF-κB) pathway by upregulating phosphorylated p65 and inducing p65 nuclear translocation, which drove M1 macrophage polarization. These findings were further confirmed using a mouse AAA model in vivo. Additionally, DEHP and MEHP promoted the proliferation and migration of primary human aortic vascular smooth muscle cells (VSMCs). Phenotypic switching of VSMCs was markedly accelerated following DEHP and MEHP treatment, potentially through the PI3K-AKT pathway, as characterized by reducing contractile markers (ACTA2 and CNN1) and enhancing proliferative markers (PCNA and SPP1). Overall, our study underscores the pivotal role that DEHP plays in exacerbating AAA by promoting M1 macrophage polarization and VSMCs phenotypic switching, which provides new insights into the adverse health effects of environmental pollution-relevant cardiovascular disease progression.
研究领域:
环境毒理学
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心血管疾病
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分子生物学
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免疫学
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细胞生物学
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PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Siyang Liu,Liying Yao,Yumeng Wang,Yi Li,Yanju Jia,Yueyue Yang,Na Li,Yuanjing Hu,Deling Kong,Xianhao Dong,Kai Wang,Meifeng Zhu
The inertness of synthetic polymer materials and the insufficient mechanical strength of reprocessed decellularized extracellular matrix (dECM) limited their promotive efforts on tissue regeneration. Here, we prepared a hybrid scaffold composed of PCL microfibers and human placental extracellular matrix (pECM) nanofibers by co-electrospinning, which was grafted with heparin and further absorbed with IL-4. The hybrid scaffold with improved hemocompatibility firstly switched macrophages to anti-inflammatory phenotype (increased by 18.1%) and then promoted migration, NO production, tube formation of endothelial cells (ECs), and migration and maturation of vascular smooth muscle cells (VSMCs), and ECM deposition in vitro and in vivo . ECs coverage rate increased by 8.6% and the thickness of the smooth muscle layer was 1.8 times more than PCL grafts at 12 wks. Our study realized the complementary advantages of synthetic polymer materials and dECM materials, and opened intriguing perspectives for the design and construction of small-diameter vascular grafts (SDVGs) and immune-regulated materials for other tissue regeneration.
研究领域:
生物材料
·
组织工程
·
血管生物学
·
免疫学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）