Nature Cardiovascular Research
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2025
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IF 10.8
Zhang Jingjing,Tang Yuyi,Zhang Shan,Xie Zhuxin,Ma Wenrui,Liu Shaowen,Fang Yixuan,Zheng Shufen,Huang Ce,Yan Guoquan,Abudupataer Mieradilijiang,Xin Yue,Zhu Jingqiao,Han Wenjing,Wang Weizhong,Shen Fenglin,Lai Hao,Liu Yang,Ye Dan,Yu Fa-Xing,Xu Yanhui,Pan Cuiping,Wang Chunsheng,Zhu Kai,Zhang Weijia
Thoracic and abdominal aortic aneurysm poses a substantial mortality risk in adults, yet many of its underlying factors remain unidentified. Here, we identify mitochondrial nicotinamide adenine dinucleotide (NAD)⁺ deficiency as a causal factor for the development of aortic aneurysm. Multiomics analysis of 150 surgical aortic specimens indicated impaired NAD + salvage and mitochondrial transport in human thoracic aortic aneurysm, with expression of the NAD + transporter SLC25A51 inversely correlating with disease severity and postoperative progression. Genome-wide gene-based association analysis further linked low SLC25A51 expression to risk of aortic aneurysm and dissection. In mouse models, smooth muscle-specific knockout of Nampt , Nmnat1 , Nmnat3 , Slc25a51 , Nadk2 and Aldh18a1 , genes involved in NAD + salvage and transport, induced aortic aneurysm, with Slc25a51 deletion producing the most severe effects. Using these models, we suggest a mechanism that may explain the disease pathogenesis: the production of type III procollagen during aortic medial matrix turnover imposes a high demand for proline, an essential amino acid component of collagen. Deficiency in the mitochondrial NAD⁺ pool, regulated by NAD⁺ salvage and transport, hinders proline biosynthesis in mitochondria, contributing to thoracic and abdominal aortic aneurysm.
研究领域:
心血管疾病
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分子生物学
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遗传学
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病理生理学
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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
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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
STAR Protocols
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2025
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IF 1.3
Hongyu Xu,Zetian Jia,Junhui Liu,Runming Liu,Wei Wei,Xiang Li
Summary Gut-microbiome-combined metabolomics studies in cerebrovascular disease highlight the microbiota-gut-brain axis in neurological disorders. Here, we present a protocol for correlating the gut microbiome and metabolomics in patients with intracranial aneurysms. We describe steps for sample collection, fecal genomic DNA extraction, rRNA PCR amplification, sequencing library construction, and rRNA sequencing. We then detail procedures for metabolite extraction, liquid chromatography-tandem mass spectrometry (LC-MS/MS) non-targeted metabolomics sequencing, and ELISA for cerebrospinal fluid and plasma samples. Finally, we perform combined multi-omics analysis. For complete details on the use and execution of this protocol, please refer to Xu et al. 1
研究领域:
神经病学
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微生物组学
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代谢组学
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DOI
PubMed
高影响因子
iScience
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2025
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IF 4.1
Haipeng He,Lei Chen,Jiaxin Peng,Jinyan Guo,Xue Xiao,Chaoxun Dou,Huining Chen,Songbiao Zhan,Xue Han,Weifeng Yao
Oxidative stress, particularly ROS accumulation, plays a key role in the development of abdominal aortic aneurysm (AAA). Surgical treatments and current drugs for AAA have limitations, including lack of specificity and significant side effects. This study constructed ROS-responsive nanoparticles using phenylthio-modified dendritic polylysine (PDP) loaded with selenomethionine (PDPs-Se) for AAA treatment, and elucidated its mechanism of action. In-vitro studies revealed that PDPs-Se enhanced the clearance of ROS by increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) while reducing malondialdehyde (MDA) levels. Furthermore, PDPs-Se upregulated the expression levels of GPX4, SLC7A11, and FTH1 to suppress ferroptosis and modulate the differentiation of vascular smooth muscle cells (VSMCs) from a synthetic to a contractile phenotype. In-vivo experiments revealed that PDPs-Se attenuated the progression of AAA by inhibiting oxidative stress responses and improving the aortic wall thickness, indicating its potential as an approach for AAA therapy.
研究领域:
医学
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生物化学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Du Chen,Tiantian Song,Yi Liu,Ying Wang,Boyang Qin,Qingyi Zhang,Weipeng Hu,Xiqiao Zhou,Rong Qi
Endovascular aneurysm repair (EVAR) plays a crucial role in the treatment of abdominal aortic aneurysm (AAA) in the clinic, but the aneurysm remains in the patient's body after surgery, continuing to pose a risk of progression. Cycloastragenol (CAG) is proven to be an effective anti-AAA drug, and its vascular protective effects can be further improved when the hydrophobic CAG is encapsulated into nano-sized formulations to enhance its bioavailability. In this context, this study developed an extravascular patch hydrogel loaded with CAG nanostructured lipid carriers and a hydrophilic drug of doxycycline hydrochloride (DOX). The extravascular patch delivered onto the mouse abdominal aortas can promote local permeation of hydrophilic/hydrophobic drugs at the vessel sites and provide effective vascular protection against AAA injury induced by elastase. This study introduces a novel and promising approach for AAA treatment, which can serve as a supplementary strategy after EVAR surgery.
研究领域:
生物医学工程
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药剂学
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血管外科
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DOI
PubMed
高影响因子
LANGMUIR
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2023
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IF 3.9
Yuting Zhu,Kai Li,Qiang Zhang,Yifeng Nie,Tun Yan,Xiaoli Shi,Dong Han
Injectable hydrogels with strong mechanical properties have significant potential for biomedical applications, including the development of electronic skin, intelligent medical robots, as well as tissue engineering. In this study, we report on an injectable hydrogel with notable tensile strength and adhesion properties, achieved through cross-linking thiol-terminated four-arm poly (ethylene glycol) using silver-doped nano-hydroxyapatite, modified with dopamine. Subsequently, the hydrogel was injected in vivo through the perivascular interstitial space of rats. The hydrogel wrapped around the damaged abdominal aortic adventitia, which greatly increases the stress strength of the arterial adventitia. We found that the hydrogel was characterized by excellent biocompatibility, and it induced little immune response over a span of 21 days post-implantation. This simple and minimally invasive vascular protection strategy appears promising for the treatment of vascular diseases, such as abdominal aortic aneurysm (AAA).
研究领域:
生物医学工程
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组织工程
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血管外科
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Jiahao Lei,Xunzhong Dong,Yong Huang,Zhaoyu Wu,Zhiyou Peng,Bo Li,Ruihua Wang,Ying Pan,Xiangtao Zheng,Zhen Zhao,Xinwu Lu
The abdominal aortic aneurysm (AAA) is a severe and complex condition characterized by the pathological dilation of the abdominal aorta. Current therapeutic strategies are limited, with surgical repair being the most effective intervention due to the lack of medications that can slow aneurysmal expansion or prevent adverse events. In this study, an innovative nanoplatform, Mn-UiO-66-NH 2 @HA, designed to repair vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM) is developed, thereby enhancing arterial wall integrity. This nanoplatform utilizes the classic metal-organic framework (MOF) UiO-66-NH 2 , doped with manganese ions (Mn 2+ ) and coated with hyaluronate tetrasaccharide (4-mer HA). The Mn-UiO-66-NH 2 @HA nanoparticles demonstrates excellent drug-loading efficiency, sustained release properties, and biocompatibility. In vitro, these nanoparticles significantly increases VSMC contractility and up-regulated elastin and lysyl oxidase expressions, crucial for ECM repair, while inhibiting matrix metalloproteinases. In vivo studies on an Ang II-induced AAA mouse model reveals that Mn-UiO-66-NH 2 @HA effectively reduces aneurysmal expansion and improves aortic structural integrity. This study presents a promising co-delivery system leveraging MOF carriers coated with 4-mer HA and Mn 2+ , offering a novel therapeutic strategy for the treatment and management of AAA.
研究领域:
生物医学工程
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心血管病学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Yang Zhang,Sijie Cheng,Yu He,Chaojie Tang,Feng Liu,Yun Sun,Shuo Zhao,Greta S. P. Mok,Hong Yang,Zhiguo Zhou,Wu Wang
Thrombosis is closely related to the instability of intracranial aneurysm (IA), whose rupture is associated with high morbidity and mortality. It is difficult to detect an IA-related thrombus because traditional magnetic resonance imaging (MRI) and even contrast-enhanced MRI cannot clearly distinguish a thrombus from the surrounding tissues. Herein, a nanoplatform [(MFe2O4–ZnDPA nanoparticles (NPs)], consisting of Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 NPs for imaging and Zn(II)-bis(dipicolylamine) (ZnDPA) for thrombus targeting, is constructed to target an experimental aneurysm-related thrombus in rabbits via MRI. In vitro experiments including platelet safety evaluation primarily prove that MFe2O4–ZnDPA NPs with a high MRI transverse relaxation time (T2) have good biocompatibility. MFe2O4–ZnDPA NPs could target a thrombus via the special interaction between ZnDPA and phosphatidylserine of activated platelets in the thrombus through MRI and Fe quantification assays. Moreover, after MFe2O4–ZnDPA NPs are injected into the ear vein of common carotid artery aneurysm model rabbits, MRI shows that MFe2O4–ZnDPA NPs could accumulate in the aneurysm-related thrombus from 0 to 15 min after injection and decrease in the next 45 min. Meanwhile, MFe2O4–ZnDPA NPs could decrease the MRI T2 signal of the aneurysm-related thrombus to enhance the outline of the aneurysm. This study demonstrates that a nanoplatform can enhance the detection of an aneurysm-related thrombus as well as aneurysm itself to assist further treatment of IA.
研究领域:
医学成像
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纳米技术
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神经病学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2023
·Vol. 14
·期 1
·1-19
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IF 16.6
Da Xingwen,Li Ziyan,Huang Xiaofan,He Zuhan,Yu Yubing,Tian Tongtong,Xu Chengqi,Yao Yufeng,Wang Qing K.
Thoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1 C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1 +/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1 smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1 +/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1.
研究领域:
心血管疾病
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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
Bioengineering & Translational Medicine
·
2025
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IF 5.7
Lulu Chen,Bicheng Chen,Xiang Su
An abdominal aortic aneurysm (AAA) is a life-threatening vascular condition characterized by the dilation of the abdominal aorta, with ferroptosis playing a significant role in its pathogenesis. This study investigates the therapeutic potential of engineering biomimetic nanovesicles to deliver phosphatidylethanolamine-binding protein 1 (PEBP1) mRNA for inhibiting ferroptosis in vascular smooth muscle cells (VSMCs) and preventing AAA progression. Differential gene expression analysis of the AAA transcriptomic dataset GSE57691 identified 243 differentially expressed genes (DEGs), intersecting with 12 ferroptosis-related genes. Single-cell analysis of dataset GSE237230 highlighted PEBP1 as a key gene in VSMCs. Overexpression of PEBP1 in VSMCs enhanced proliferation, reduced reactive oxygen species (ROS) and iron levels, and inhibited apoptosis and ferroptosis via the NRF2/GPX4 axis. The engineered biomimetic nanovesicles demonstrated significant uptake by VSMCs and effective delivery of PEBP1 mRNA. In vivo studies confirmed that these nanovesicles substantially inhibited AAA progression in mice. This study presents a novel bioengineering approach for AAA treatment by targeting ferroptosis through PEBP1 mRNA delivery, offering a promising molecular strategy for the prevention and management of AAA.
研究领域:
生物医学工程
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纳米技术
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分子生物学
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心血管疾病研究
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基因治疗
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产品关联
DOI
PubMed
高影响因子
International Journal of Medical Sciences
·
2024
·
IF 3.2
Mi Tang,Min Wang,Zhirong Wang,Bo Jiang
Aortic aneurysm and dissection (AD) represent a critical cardiovascular emergency with an alarmingly high mortality rate. Recent research has spotlighted the overexpression of genes associated with the m6A modification in AD patients, linking them to the presence of inflammatory M1-type macrophages. Moreover, glycolysis is widely recognized as a key feature of inflammatory M1-type macrophages, but biomarkers linking glycolysis and macrophage function to promote disease progression in AD have not been reported. We conducted an analysis of aortic immune cell infiltration, macrophages, and m6A-related biomarkers in AD patients using bioinformatics techniques. Subsequently, we employed a combination of RT-PCR, WB, and immunofluorescence assays to elucidate the alterations in the expression of M1- and M2-type macrophages, as well as markers of glycolysis, following the overexpression of key biomarkers. These findings were further validated in vivo through the creation of a rat model of AD with knockdown of the aforementioned key biomarkers. The findings revealed that the m6A-modified related gene RBM15 exhibited heightened expression in AD samples and was correlated with macrophage polarization. Upon overexpression of RBM15 in macrophages, there was an observed increase in the expression of M1-type macrophage markers CXCL9 and CXCL10, alongside a decrease in the expression of M2-type macrophage markers CCL13 and MRC1. Furthermore, there was an elevation in the expression of glycolytic enzymes GLUT1 and Hexokinase, as well as HIF1α, GAPDH, and PFKFB3 after RBM15 overexpression. Moreover, in vivo knockdown of RBM15 led to an amelioration of aortic aneurysm in the rat AD model. This knockdown also resulted in a reduction of the M1-type macrophage marker iNOS, while significantly increasing the expression of the M2-type macrophage marker CD206. In conclusion, our findings demonstrate that RBM15 upregulates glycolysis in macrophages, thus contributing to the progression of AD through the promotion of M1-type macrophage polarization. Conversely, downregulation of RBM15 suppresses M1-type macrophage polarization, thereby decelerating the advancement of AD. These results unveil potential novel targets for the treatment of AD.
研究领域:
心血管疾病
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免疫学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
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