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Mechanobiology in vascular remodeling

National Science Review 2018年第6期5卷 933-946页

作者： Yue Han Kai Huang Qing-Ping Yao Zong-Lai Jiang Institute of Mechanobiology & Medical Engineering School of Life Sciences & BiotechnologyShanghai Jiao Tong University School of Biological Science & Medical Engineering Beijing Advanced Innovation Center for Biomedical Engineering Beihang University

vascular remodeling is a common pathological process in cardiovascular diseases and includes changes in cell proliferation, apoptosis and differentiation as well as vascular homeostasis. Mechanical stresses, such as shear stress and cyclic stretch, play an important role in vascular remodeling. vascular cells can sense the mechanical factors through cell membrane proteins, cytoskeletons and nuclear envelope proteins to initiate mechanotransduction, which involves intercellular signaling, gene expression, and protein expression to result in functional regulations. Non-coding RNAs, including micro RNAs and long non-coding RNAs, are involved in the regulation of vascular remodeling processes. Mechanotransduction triggers a cascade reaction process through a complicated signaling network in cells. High-throughput technologies in combination with functional studies targeting some key hubs and bridging nodes of the network can enable the prioritization of potential targets for subsequent investigations of clinical translation. vascular mechanobiology, as a new frontier field of biomechanics, searches for principles of stress-growth in vasculature to elucidate how mechanical factors induce biological effects that lead to vascular remodeling,with the goal of understanding the mechanical basis of the pathological mechanism of cardiovascular diseases at the cellular and molecular levels. vascular mechanobiology will play a unique role in solving the key scientific problems of human physiology and disease, as well as generating important theoretical and clinical results.

关键词： mechanobiology vascular remodeling cardiovascular disease mechanotransduction endothelial cell vascular smooth muscle cell nuclear envelope microRNA

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Mechanistic insight into lysyl oxidase in vascular remodeling and angiogenesis

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Genes & Diseases 2023年第3期10卷 771-785页

作者： Zhao-Jun Wang Qi-Wen Guan Hong-Hao Zhou Xiao-Yuan Mao Fang-Hui Chen Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Institute of Clinical Pharmacology Central South UniversityHunan Key Laboratory of PharmacogeneticsChangshaHunan 410078China Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of EducationChangshaHunan 410078China National Clinical Research Center for Geriatric Disorders ChangshaHunan 410008China Department of Pharmacy The First Affliated Hospital of Gannan Medical UniversityGanzhouJiangxi 341000China

vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis.

关键词： Angiogenesis Disease pathology Lysyl oxidase Therapeutic target vascular homeostasis vascular remodeling

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Current knowledge of Krüppel-like factor 5 and vascular remodeling: providing insights for therapeutic strategies

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Journal of Molecular Cell Biology 2021年第2期13卷 79-90页

作者： Ziyan Xie Junye Chen Chenyu Wang Jiahao Zhang Yanxiang Wu Xiaowei Yan Department of Cardiology Peking Union Medical College HospitalPeking Union Medical College&Chinese Academy of Medical SciencesBeijing 100730China Department of vascular Surgery Peking Union Medical College HospitalPeking Union Medical College&Chinese Academy of Medical SciencesBeijing 100730China

vascular remodeling is a pathological basis of various disorders. Therefore, it is necessary to understand the occurrence, prevention, and treatment of vascular remodeling. Krüppel-like factor 5 (KLF5) has been identified as a significant factor in cardiovascular diseases during the last two decades. This review provides a mechanism network of function and regulation of KLF5 in vascular remodeling based on newly published data and gives a summary of its potential therapeutic applications. KLF5 modulates numerous biological processes, which play essential parts in the development of vascular remodeling, such as cell proliferation, phenotype switch, extracellular matrix deposition, inflammation, and angiogenesis by altering downstream genes and signaling pathways. Considering its essential functions, KLF5 could be developed as a potent therapeutic target in vascular disorders.

关键词： Krüppel-like factor 5(KLF5) vascular remodeling inflammation angiogenesis drug development microRNA

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A bioactive compliant vascular graft modulates macrophage polarization and maintains patency with robust vascular remodeling

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Bioactive Materials 2023年第1期19卷 167-178页

作者： Alexander Stahl Dake Hao Janos Barrera Dominic Henn Sien Lin Seyedsina Moeinzadeh Sungwoo Kim William Maloney Geoffrey Gurtner Aijun Wang Yunzhi Peter Yang Department of Orthopaedic Surgery Stanford University240 Pasteur DriveStanfordCA94304USA Department of Chemistry Stanford University121 Mudd BuildingStanfordCA94305USA Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817USA Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817USA Department of Surgery Stanford University300 Pasteur DriveStanfordCA94305USA Department of Biomedical Engineering University of California DavisDavisCA95616USA Department of Materials Science and Engineering Stanford University496 Lomita MallStanfordCA94305USA Department of Bioengineering Stanford University443 Via OrtegaStanfordCA4305USA

Conventional synthetic vascular grafts are associated with significant failure rates due to their mismatched mechanical properties with the native vessel and poor regenerative *** different tissue engineering approaches have been used to improve the biocompatibility of synthetic vascular grafts,it is still crucial to develop a new generation of synthetic grafts that can match the dynamics of native vessel and direct the host response to achieve robust vascular *** size of pores within implanted biomaterials has shown significant effects on macrophage polarization,which has been further confirmed as necessary for efficient vascular formation and ***,we developed biodegradable,autoclavable synthetic vascular grafts from a new polyurethane elastomer and tailored the grafts’interconnected pore sizes to promote macrophage populations with a pro-regenerative phenotype and improve vascular regeneration and patency *** synthetic vascular grafts showed similar mechanical properties to native blood vessels,encouraged macrophage populations with varying M2 to M1 phenotypic expression,and maintained patency and vascular regeneration in a one-month rat carotid interposition model and in a four-month rat aortic interposition *** innovative bioactive synthetic vascular graft holds promise to treat clinical vascular diseases.

关键词： vascular graft vascular compliance Pore size Macrophage polarization vascular remodeling

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ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4840-4855页

作者： Junting Zhang Yiying Li Jianchao Zhang Lu Liu Yuan Chen Xusheng Yang Xueyi Liao Muhua He Zihui Jia Jun Fan Jin-Song Bian Xiaowei Nie Shenzhen Institute of Respiratory Disease Shenzhen Key Laboratory of Respiratory DiseaseShenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Afiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China Post-Doctoral Scientific Research Station of Basic Medicine JinanUniversityGuangzhou 510632China Department of Pharmacology School of MedicineSouthern University of Science and TechnologyShenzhen 518055China Lung Transplant Group Wuxi People's Hospital Affliated to Nanjing Medical UniversityWuxi 211103China Department of Medical Biochemistry and Molecular Biology School of MedicineJinan UniversityGuangzhou 510632China

Pulmonary hypertension(PH)is an extremely malignant pulmonary vascular disease of unknown ***1 is an RNA editing enzyme that converts adenosine in RNA to inosine,thereby affecting RNA ***,the role of ADAR1 in PH development remains *** the present study,we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular *** of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells(PASMCs).Conversely,inhibition of ADAR1 produced opposite ***-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in ***17 level was significantly lowered in the serum of PH *** effects of ADAR1 on cell cycle progression and proliferation were mediated by ***1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from mlA *** demonstrate for the first time that ADAR1 contributes to the PH development,at least partially,through m1A modification of circCDK17 and the subsequent PASMCs *** study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

关键词： Pulmonary hypertension ADAR1 Circular RNA vascular remodeling Cell proliferation

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vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout mice

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Chinese Medical Journal 2008年第3期121卷 220-226页

作者： XU Yang ARAI Hidenori MURAYAMA Toshinori KITA Toru YOKODE Masayuki Institute of Medicinal Plant Development Chinese Academy ofMedical Sciences and Peking Union Medical College Beijing100094 China Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Department of Geriatric Medicine Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Department of Cardiovascular Medicine Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Translational Research Center Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan

Background vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis, postangioplasty restenosis and transplant arteriopathy. Recently, pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis. But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not yet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene （LDL-/-） and expressing ubiquitously green fluorescent protein （GFP） were obtained by cross-breeding LDL -/- mice with the GFP-expressing transgenic mice. LDL-/- mice （22-24 weeks of age） fed high fat diet containing 1.25% （w/w） cholesterol were subjected to 9Gy irradiation and received bone marrow （BM） cells from the double-transgenic mice. Four weeks later, a nonconstrictive cuff was placed around the right femoral artery. After another 2 weeks, both right and left femoral arteries were harvested and subjected to histochemical analysis. Apoptosis was analyzed in situ using TUNEL assay. Results Two weeks after cuff placement, atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells. The tissue stained with anti-α smooth muscle actin （SMA） antibody, showed a number of SMA-positive cells in the intimal lesion area. They were also positive for GFP, indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions. Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP. The intima and media showed a large number of TUNEL-positive signals after 2 weeks cuff injury, indicating the presence of apoptosis in vascular remodeling. Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular injury under the hypercholes

关键词： vascular remodeling macrophage smooth muscle cell endothelial cell bone marrow

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Sang-Yod rice bran hydrolysates alleviate hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in nitric oxide deficient hypertensive rats

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Asian Pacific Journal of Tropical Biomedicine 2021年第1期11卷 10-19页

作者： Gulladawan Jan-On Akarachai Tubsakul Weerapon Sangartit Poungrat Pakdeechote Veerapol Kukongviriyapan Ketmanee Senaphan Chakree Thongraung Upa Kukongviriyapan Department of Physiology Faculty of MedicineKhon Kaen UniversityKhon KaenThailand School of Medicine Walailak UniversityNakhon Si ThammaratThailand Department of Pharmacology Faculty of MedicineKhon Kaen UniversityKhon KaenThailand Division of Physiology Faculty of Veterinary MedicineKhon Kaen UniversityKhon KaenThailand Department of Food Technology Faculty of Agro-IndustryPrince of Songkla UniversitySongklaThailand

Objective:To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates(SRH)and in combination with lisinopril against hypertension,endothelial dysfunction,vascular remodeling,and oxidative stress in rats with nitric oxide deficiency-induced ***:Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor,Nω-nitro-L-arginine methyl ester(L-NAME)in drinking water for 6 *** rats were administered daily with SRH(500 mg/kg/day),lisinopril(1 mg/kg/day),or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME *** status,vascular reactivity to vasoactive agents,and vascular remodeling were *** and aortic tissues were collected for measurements of oxidative stress markers,plasma angiotensin-converting enzyme(ACE)activity,plasma angiotensinⅡ,and protein ***:L-NAME induced remarkable hypertension and severe oxidative stress,and altered contents of smooth muscle cells,elastin,and collagen of the aortic *** or lisinopril alone reduced blood pressure,restored endothelial function,decreased plasma ACEs and angiotensinⅡlevels,alleviated oxidant markers and glutathione redox status,and restored the vascular *** effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91phox and AT1R *** combination of SRH and lisinopril was more effective than ***:SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

关键词： Sang-Yod rice bran hydrolysates Hypertension Endothelial dysfunction Oxidative stress vascular remodeling

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ACE2/Ang-(1-7) signaling and vascular remodeling

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Science China(Life Sciences) 2014年第8期57卷 802-808页

作者： ZHANG ZhenZhou CHEN LaiJiang ZHONG JiuChang GAO PingJin OUDIT Gavin Y. State Key Laboratory of Medical Genomics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Hypertension Shanghai Institute of Hypertension Department of Medicine University of Alberta Mazankowski Alberta Heart Institute

The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and *** of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and *** converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular ***,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the *** addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular *** present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.

关键词： angiotensin converting enzyme 2 inflammation vascular remodeling angiotensin II oxidative stress

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Mineralocorticoid receptor: a critical player in vascular remodeling

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Science China(Life Sciences) 2014年第8期57卷 809-817页

作者： DUAN ShengZhong Key Laboratory of Nutrition and Metabolism Institute for Nutritional SciencesShanghai Institutes for Biological SciencesChinese Academy of Sciences

vascular remodeling is a pathological condition with structural changes of blood *** inside-out and outside-in hypothesis have been put forward to describe mechanisms of vascular *** integrated model of these two hypotheses emphasizes the importance of immune cells such as monocytes/macrophages,T cells,and dendritic *** immune cells are at the center stage to orchestrate cellular proliferation,migration,and interactions of themselves and other vascular cells including endothelial cells(ECs),vascular smooth muscle cells(VSMCs),and *** changes on vascular wall lead to inflammation and oxidative stress that are largely responsible for vascular *** receptor(MR)is a classic nuclear *** agonist promotes inflammation and oxidative stress and therefore exacerbates vascular ***,MR antagonists have the opposite *** has direct roles on vascular cells through non-genomic or genomic actions to modulate inflammation and oxidative *** studies using genetic mouse models have revealed that MR in myeloid cells,VSMCs and ECs all contribute to vascular *** conclusion,data in the past years have demonstrated that MR is a critical control point in modulating vascular *** will continue to provide evidence with more detailed mechanisms to support this notion.

关键词： vascular remodeling mineralocorticoid receptor immune cell endothelial cell vascular smooth muscle cell fibroblast

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Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

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Traditional Medicine Research 2024年第2期9卷 52-65页

作者： Yu-Ming Wang Hong-Wei Tao Feng-Chan Wang Ping Han Na Liu Guo-Jing Zhao Hai-Bo Hu Xue-Chao Lu College of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Respiratory and Critical Care Medicine Qingdao Hospital of Traditional Chinese Medicine(Qingdao Hiser hospital)Qingdao 266000China.

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and *** clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains ***:In this study,a monocrotaline-induced PAH rat model was established and treated with *** therapeutic effects of MFJT on PAH rat model were *** pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried *** key targets identified from network pharmacology were ***:Results showed significant therapeutic effects of MFJT on PAH rat *** of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular *** docking showed that the key components were well docked with the core *** experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

关键词： Mufangji tang pulmonary arterial hypertension apoptosis inflammatory response oxidative stress vascular remodeling

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