Aging and Disease
·
2024
·
IF 7
Li Li,Paul R. Krafft,Na Zeng,Ranran Duan,Xiang Qi,Anwen Shao,Fushan Xue,John H. Zhang
Ischemic stroke can be a serious complication of selective carotid endarterectomy (CEA) in patients with carotid artery stenosis (CAS). The underlying risk factors and mechanisms of these postoperative strokes are not completely understood. Our previous study showed that TMEM166-induced neuronal autophagy is involved in the development of secondary brain injury following cerebral ischemia-reperfusion injury in rats. This current study aimed to investigate the role of TMEM166 in ischemic stroke following CEA. In the clinical part of this study, the quantitative analysis demonstrated circulating TMEM166, interleukin 6 (IL-6), and C-reactive protein (CRP) levels were significantly elevated in patients who suffered an ischemic stroke after CEA compared to those who did not. Furthermore, non-survivors exhibited higher levels of these proteins than survivors. In the preclinical part of this study, a middle cerebral artery occlusion (MCAO) model was implemented following CAS simulation in TMEM166 -/- mice. We found TMEM166 expression was positively correlated with the degree of ischemic brain injury. Ad5-TMEM166 transfection aggravated ischemic brain injury by inducing microglial autophagy activation and release of inflammatory cytokines. Accordingly, TMEM166 deficiency reduced brain inflammation and inhibited excessive microglial autophagy through the mammalian target of rapamycin (mTOR) pathway. These findings suggest that TMEM166 may play a key role in the development of ischemic injury after CEA and may serve as a biomarker for risk assessment of postoperative ischemic stroke.
研究领域:
神经科学
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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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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
·
2025
·
IF 3.3
Xiaoyu Wu,Chuanbo Ding,Xinglong Liu,Qiteng Ding,Shuai Zhang,Yue Wang,Ting Zhao,Wencong Liu
Carotid atherosclerosis (CAS) is a complex cardiovascular disease linked to inflammatory response and oxidative stress. This study aimed to develop and assess the therapeutic efficacy of Phlorizin liposomes (Phlorizin-Lips) in repairing CAS in rats. Phlorizin-Lips were prepared using the film dispersion method and evaluated for controlled release, antioxidant properties, and biocompatibility. The methodology included preparing Phlorizin-Lips, conducting in vitro and in vivo experiments, observing histopathological changes in carotid arteries in a rat model, and detecting inflammatory markers and antioxidant gene expression in arterial endothelial cells using immunoblotting and ELISA. Results showed that Phlorizin-Lips significantly lowered inflammatory markers TNF-α and IL-1β in endothelial cells while upregulating Nrf2 and its downstream antioxidant genes, enhancing the cells' antioxidant capacity and reducing oxidative damage by activating the Nrf2 signaling pathway. Additionally, Phlorizin-Lips reduced carotid plaque formation, improved vascular endothelial function, and promoted CAS repair. This study underscores Phlorizin's potential as a therapeutic agent for CAS and highlights the Nrf2 pathway's role in regulating inflammation and oxidative stress. Future research will explore the clinical potential of Phlorizin-Lips.
研究领域:
药理学
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心血管病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2025
·
IF 2.7
Bin Xu,Yifei Zheng,Yi Wang,Jie Sun,Dehai Lang,Qiyang Xu
Aquaporin 9 (AQP9) expression is significantly elevated in vulnerable carotid plaque (VCP). Hence, we probed the mechanism of AQP9 in VCP formation. The VCP model was established in ApoE −/− C57BL/6 mice. Dataset GSE163154 was analyzed by R software. Human aortic endothelial cells (HAECs) were incubated with 50 µg/mL oxidized low-density lipoprotein (ox-LDL) and 20 mM l -(+)-lactic acid for 24 h. Mice (AQP9 overexpression plasmid) and HAECs (AQP9 overexpression/dynamin-related protein 1 [DRP1] silencing plasmids) were infected by lentivirus. Mouse plasma lipid level was estimated. The histopathological condition of model mice was observed by oil red lipid staining, hematoxylin–eosin (H&E) staining, and Masson staining. Levels of AQP9 and DRP1 in model mice and HAECs were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Levels of AQP9, DRP1, and mitochondrial fission-/endothelium–mesenchymal transition (EndMT)-related factors in model mice and HAECs were assayed by western blot. Lactate level in model mice was detected. Promoter histone lactylation level of DRP1 was measured by chromatin immunoprecipitation (ChIP). Behaviors of HAECs were tested by cell counting kit-8 (CCK-8), colony formation test, and scratch test. AQP9 was highly expressed in intraplaque hemorrhage patients. AQP9 overexpression promoted levels of DRP1, lactate, histone lactylation, mitochondrial fission factor, vimentin, and N -cadherin, while inhibiting vascular endothelial (VE)-cadherin level and plaque stability in model mice and facilitating viability, proliferation, and migration of HAECs. DRP1 silencing reversed the impacts of AQP9 overexpression on cell viability, proliferation, migration, and levels of mitochondrial fission-/EndMT-related factors in HAECs. AQP9 enhances DRP1-mediated mitochondrial fission by lactate and thus promotes EndMT to exacerbate the VCP formation.
研究领域:
医学
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分子生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Mo Xinhai,Yan Fei,Zhang Bo
Cardiovascular intervention is a common treatment procedure for many cardiovascular diseases. But restenosis often occurs after these procedures, greatly discounting their long-term therapeutic effects. Early detection of endothelial denudation is helpful for the diagnosis and prevention of restenosis. Here, we fabricated targeted microbubbles by conjugating anti-collagen IV antibodies to the surface of biotinylated microbubbles (MBColIV) and applied them for ultrasound molecular imaging of endothelial injury at early stage. Our results showed that the MBColIV, with a typical multi-peak particle distribution, was successfully constructed, which was confirmed by Alexa Fluor® 555-labeled secondary antibody. Ex vivo adhesion of microbubbles revealed that MBColIV can effectively and specially bind to the surface of balloon-injured carotid artery. The in vivo animal experiments showed ultrasound molecular imaging signals from carotid artery-injured rats administrated with MBColIV were significantly higher than those administrated with isotype control microbubbles. Histological staining of the left carotid common artery revealed that collagen IV was obviously exposed after endothelium denudation in balloon-injured artery. In conclusion, our current study provides an effective approach to detect vascular injury at the early stage and a potential platform for image-guided therapy to vascular injury.
研究领域:
医学影像学
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心血管病学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Feiran Zhou,Xinyi Hu,Weijing Feng,Minghui Li,Bin Yu,Chenxing Fu,Caiwen Ou
Intimal hyperplasia-induced restenosis is a common response to vascular endothelial damage caused by mechanical force or other stimulation, and is closely linked to vascular remodeling . Curcumin , a traditional Chinese medicine , exhibits potent protective effects in cardiovascular diseases; for example, it attenuates vascular remodeling. Although the suppressive effects of curcumin on diseases caused by vascular narrowing have been investigated, the underlying mechanisms remain unknown. Long non-coding RNAs (lncRNAs) regulate various pathological processes and affect the action of drugs. In the present study, we found that the curcumin remarkably downregulated the expression of lncRNA H19 and thereby inhibited intimal hyperplasia-induced vascular restenosis. Furthermore, the inhibition of the expression of H19 by curcumin resulted in the inactivation of the Wnt/β-catenin signaling. Overall, we show that curcumin suppresses intimal hyperplasia via the H19/Wnt/β-catenin pathway, implying that H19 is a critical molecule in the suppression of intimal hyperplasia after balloon injury by curcumin. These insights should be useful for potential application of curcumin as a therapeutic intervention in vascular stenosis.
研究领域:
分子生物学
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药理学
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心血管疾病
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产品关联
DOI
PubMed
高影响因子
CELLULOSE
·
2020
·Vol. 27
·期 6
·3443-3453
·
IF 4.21
Wang Yamei,Xiao Dongdong,Zhong Yi,Zhang Linping,Chen Zhize,Sui Xiaofeng,Wang Bijia,Feng Xueling,Xu Hong,Mao Zhiping
Abstract Achieving effective hemostasis is significant to ensure the survival of the people with acute massive bleeding in the battlefield or daily life in pre-hospital care. In this work, modified cotton fabric with asymmetric wettability (Janus) was prepared using a fast and simple spray-coating strategy, where, one side of the fabric was sprayed with carboxymethyl chitosan solution to achieve hydrophilicity (0°) while the other side with hydrophobicity (152°) was built using paraffin. The hydrophilic surface could provide blood absorption and promote hemostasis, while the hydrophobic surface prevented the excessive blood absorption. The hemostatic efficiency of fabrics was tested in vitro and in vivo. Here, the carboxymethyl chitosan coated carboxymethylated cotton (CS-MCF) and Janus showed better hemostatic capacity than the cotton fabric (CF) in vitro with the lower blood clotting index. Furthermore, the Janus had better hemostatic performance than CF in rat liver animal model, and prolonged the survival time of the rats in carotid artery animal model. Therefore, Janus, with superior hemostatic efficiency over the cotton fabric, has a bright application prospect as hemostatic wound dressing. Graphic abstract
研究领域:
材料科学
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生物医学工程
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伤口护理
·
止血
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Han Wang,Yonghao Xiao,Zhiping Fang,Yuanguo Zhang,Liu Yang,Chenyu Zhao,Zhu Meng,Yu Liu,Chongchong Li,Qianqian Han,Zengguo Feng
Cardiovascular disease has become one of the main causes of death. It is the common goal of researchers worldwide to develop small-diameter vascular grafts to meet clinical needs. Collagen is a valuable biomaterial that has been used in the preparation of vascular grafts and has shown good results. Recombinant humanized collagen (RHC) has the advantages of clear chemical structure, batch stability, no virus hazard and low immunogenicity compared with animal-derived collagen, which can be developed as vascular materials. In this study, Poly ( l -lactide- ε-caprolactone) with l -lactide/ε-caprolactone (PLCL) and type III recombinant humanized collagen (hCOLIII) were selected as raw materials to prepare vascular grafts, which were prepared by the same-nozzle electrospinning apparatus. Meanwhile, procyanidin (PC), a plant polyphenol, was used to cross-link the vascular grafts. The physicochemical properties and biocompatibility of the fabricated vascular grafts were investigated by comparing with glutaraldehyde (GA) crosslinked vascular grafts and pure PLCL grafts. Finally, the performance of PC cross-linked PLCL-hCOLIII vascular grafts were evaluated by rabbit carotid artery transplantation model. The results indicate that the artificial vascular grafts have good cell compatibility, blood compatibility, and anti-calcification performance, and can remain unobstructed after 30 days carotid artery transplantation in rabbits. The grafts also showed inhibitory effects on the proliferation of SMCs and intimal hyperplasia, demonstrating its excellent performance as small diameter vascular grafts.
研究领域:
生物材料
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组织工程
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血管外科
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生物医学工程
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产品关联
DOI
PubMed
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
·
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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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Jian Tang,Yang Liu,Mingxi Li,Xiao Wang,Anning Du,Ning Gu,Fang Yang
Vascular inflammation is an early manifestation and common pathophysiological basis of numerous cardiovascular and cerebrovascular diseases. However, effective surveillance methods are lacking. In this study, sulfur hexafluoride (SF 6 )-loaded polylactic acid- co -glycolic acid (PLGA) nanobubbles (NBs) with a surface assembly of cyclodextrin (CD) and sphingosine-1-phosphate (S1P) (S1P@CD-PLGA NBs) are designed. The characterization results show that S1P@CD-PLGA NBs with diameters of ≈200 nm have good stability, biosafety, and ultrasound imaging-enhancement effects. When interacting with inflammatory vascular endothelial cells, S1P molecules encapsulated in cyclodextrin cavities exhibit a rapid, excellent, and stable targeting effect owing to their specific interaction with the highly expressed S1P receptor 1 (S1PR1) on the inflammatory vascular endothelial cells. Particularly, the S1P–S1PR1 interaction further activates the downstream signaling pathway of S1PR1 to reduce the expression of tumor necrosis factor-α (TNF-α) to protect endothelial cells. Furthermore, mouse models of carotid endothelial injuries and mesenteric thrombosis demonstrate that S1P@CD-PLGA NBs have excellent capabilities for in vivo targeting imaging. In summary, this study proposes a new strategy of using S1P to target inflammatory vascular endothelial cells while reducing the expression of TNF-α, which has the potential to be utilized in the targeted surveillance and treatment of vascular inflammatory diseases.
研究领域:
心血管疾病
·
生物医学工程
·
分子生物学
·
诊疗学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 4
·2155-2162
·
IF 2.784
Tao Song,Jingdong Zhao,Tongbai Jiang,Xing Jin,Yubin Li,Xinrong Liu
The present study investigated the effects of formononetin (FMN) against balloon injury‑induced neointima formation in vivo and platelet‑derived growth factor (PDGF)‑BB‑induced proliferation and migration of vascular smooth muscle cells (VSMCs) in vitro, and explored the underlying mechanisms. A rat model of carotid artery injury was established, in order to examine the effects of FMN on balloon injury‑induced neointima formation. Histological observation of the carotid artery tissues was conducted by hematoxylin and eosin staining. VSMC proliferation during neointima formation was observed by proliferating cell nuclear antigen staining. Subsequently, rat aortic VSMCs were isolated, and the effects of FMN on PDGF‑BB‑induced VSMC proliferation and migration were determined using Cell Counting Kit‑8 and Transwell/wound healing assays, respectively. Immunohistochemical and immunocytochemical staining was applied to measure the expression of transforming growth factor (TGF)‑β in carotid artery tissues and VSMCs, respectively. SMAD family member 3 (Smad3)/phosphorylated (p)‑Smad3 expression was examined by western blotting. FMN treatment significantly inhibited the abnormal proliferation of smooth muscle cells in neointima, and alterations to the vascular structure were attenuated. In addition, pretreatment with FMN effectively inhibited the proliferation of PDGF‑BB‑stimulated VSMCs (P<0.05). FMN also reduced the number of cells that migrated to the lower surface of the Transwell chamber and decreased wound‑healing percentage (P<0.05). The expression levels of TGF‑β were decreased by FMN treatment in vivo and in vitro, and Smad3/p‑Smad3 expression was also markedly inhibited. In conclusion, FMN significantly protected against balloon injury‑induced neointima formation in the carotid artery of a rat model; this effect may be associated with the regulation of VSMC proliferation and migration through altered TGF‑β1/Smad3 signaling.
研究领域:
药理学
·
心血管疾病
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·
IF 3.9
Yong-Hao Xiao,Xin Jin,Liujun Jia,Jubo Li,Baojie Zhang,Xue Geng,Lin Ye,Aiying Zhang,Yongquan Gu,Zeng-Guo Feng
In our previous study, the pristine bilayer small-diameter in situ tissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 μm and 202 μm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneury-sms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regene-ration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 μm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.
研究领域:
组织工程
·
生物医学工程
·
血管外科
·
材料科学
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DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2021
·
IF 7.658
Shuai Chen,Keyu Lv,Anish Sharda,Jun Deng,Wanjiang Zeng,Chao Zhang,Qinghua Hu,Pengfei Jin,Guangmin Yao,Xulin Xu,Zhangyin Ming,Chao Fang
Classical antithrombotics and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. The platelet-independent fibrin generation by activated endothelium highlights the importance of vascular protection in addition to platelet inhibition in thrombosis prevention. Dihydromyricetin (DHM), the most abundant flavonoid in Ampelopsis grossedentata, has unique vasoprotective effects. This study aims to characterize the antithrombotic potential of DHM. The effects of DHM on the activation of platelets and endothelial cells were evaluated in vitro . Calcium mobilization and activation of mitogen-activated protein kinases (MAPKs) were examined as the potential targets of DHM based on molecular docking analysis. The in vivo effects of DHM were determined in FeCl 3 -injured carotid arteries and laser-injured cremasteric arterioles. The results showed that DHM suppressed a range of platelet responses including aggregation, secretion, adhesion, spreading and integrin activation, and inhibited exocytosis, phosphatidylserine exposure and tissue factor expression in activated endothelial cells. Mechanistically, DHM attenuated thrombin-induced calcium mobilization and phosphorylation of ERK1/2 and p38 both in platelets and endothelial cells. Intravenous treatment with DHM delayed FeCl 3 -induced carotid arterial thrombosis . Furthermore, DHM treatment inhibited both platelet accumulation and fibrin generation in the presence or absence of eptifibatide in the laser injury-induced thrombosis model, without prolonging ex vivo plasma coagulation or tail bleeding time. DHM represents a novel antithrombotic agent whose effects involve both inhibition of platelet activation and reduction of fibrin generation as a result of endothelial protection.
研究领域:
药理学
·
心血管研究
·
分子生物学
·
血栓
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DOI
PubMed
高影响因子
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