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World Journal of Gastroenterology 2022年第3期28卷 275-289页

作者： Andrzej S Tarnawski Amrita Ahluwalia Gastroenterology Research Department University of California Irvine and the Veterans Administration Long Beach Healthcare SystemLong BeachCA 90822United States Research Service Veterans Administration Long Beach Healthcare SystemLong BeachCA 90822United States

The coronavirus disease 2019(COVID-19)infected so far over 250 million people and caused the death of over 5 million worldwide.Aging,diabetes,and cardiovascular diseases,conditions with preexisting impaired endothelial functions predispose to COVID-19.While respiratory epithelium is the main route of virus entry,the endothelial cells(ECs)lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients.COVID-19 not only affects the lungs and respiratory system but also gastrointestinal(GI)tract,liver,pancreas,kidneys,heart,brain,and skin.blood vessels are likely conduits for the virus dissemination to these distant organs.Importantly,ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network.The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract,liver,pancreas,etc.,however,the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury,spreading to various organs,and injury healing have not been sufficiently emphasized.In the present article,we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic,significant efficacy in controlling severe COVID-19 infection.

关键词： Endothelial cells Impaired endothelial function blood vessels SARS-CoV-2 COVID-19 Cytokine storm

Advances in the differentiation of pluripotent stem cells into vascular cells

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World Journal of Stem Cells 2024年第2期16卷 137-150页

作者： Yi-Chang Jiao Ying-Xin Wang Wen-Zhu Liu Jing-Wen Xu Yu-Ying Zhao Chuan-Zhu Yan Fu-Chen Liu Department of Neurology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Research Institute of Neuromuscular and Neurodegenerative Diseases Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Mitochondrial Medicine Laboratory Qilu Hospital(Qingdao)of Shandong UniversityQingdao 266103Shandong ProvinceChina Brain Science Research Institute Shandong UniversityJinan 250012Shandong ProvinceChina

blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

关键词： Induced pluripotent stem cell blood vessels Vascular organoids Endothelial cells Smooth muscle cells Pericytes Tissue engineering vascular graft

The importance of laminin at the blood-brain barrier

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Neural Regeneration Research 2023年第12期18卷 2557-2563页

作者： Sebok K.Halder Arjun Sapkota Richard Milner San Diego Biomedical Research Institute San DiegoCAUSA

The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte endfeet.In addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell behavior.The extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior.In this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity.Finally,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.

关键词： astrocytes basement membrane blood vessels blood-brain barrier integrity dystroglycan endothelial cells inflammation integrins laminin pericytes

Molecular events in the jaw vascular unit:A traditional review of the mechanisms involved in inflammatory jaw bone diseases

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生物医学研究杂志:英文版 2023年第5期37卷 313-325页

作者： Ruyu Wang Haoran Wang Junyu Mu Hua Yuan Yongchu Pang Yuli Wang Yifei Du Feng Han Department of Oral and Maxillofacial Surgery the Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Jiangsu Province Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjingJiangsu 210029China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine NanjingJiangsu 210029China International Joint Laboratory for Drug Target of Critical Illnesses Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China Department of Orthodontics the Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China.

Inflammatory jaw bone diseases are common in stomatology,including periodontitis,peri-implantitis,medication-related osteonecrosis of the jaw,radiation osteomyelitis of the jaw,age-related osteoporosis,and other specific infections.These diseases may lead to tooth loss and maxillofacial deformities,severely affecting patients'quality of life.Over the years,the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge.Therefore,exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial for improving prognosis and developing new targeted therapies.Accumulating evidence indicates that the integrated bone formation and dysfunction arise from complex interactions among a network of multiple cell types,including osteoblast-associated cells,immune cells,blood vessels,and lymphatic vessels.However,the role of these different cells in the inflammatory process and the'rules'with which they interact are still not fully understood.Although many investigations have focused on specific pathological processes and molecular events in inflammatory jaw diseases,few articles offer a perspective of integration.Here,we review the changes and mechanisms of various cell types in inflammatory jaw diseases,with the hope of providing insights to drive future research in this field.

关键词： inflammatory diseases osteogenesis-related cells immune cells blood vessels lymphatic vessels jaw vascular unit

Relationship between atrial natriuretic peptide-immunoreactive cells and microvessels in rat gastric mucosa

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Acta Pharmacologica Sinica 2006年第2期27卷 205-211页

作者： Chun-hui LI~(2,3) Zong-wei YANG~3 Zheng-ri YIN~3 Zheng JIN~3 De-gang XING~3 Lian-hua PIAO~3 Yong-chul KIM~4 Wen-xie XU~(2,5) ~2College of Life Science and Biotechnology.Shanghai Jiaotong University,Shanghai 200240,China:~3Department of Physiology.Yanbian University College of Medicine.Yanji 133000.China ~4Department of Physiology,Chungbuk National University,College of Medicine.Cheongju.Chungbuk 361-763,Korea College of Life Science and Biotechnology Shanghai Jiaotong University Shanghai China Department of Physiology Yanbian University College of Medicine Yanji China Department of Physiology Chungbuk National University College of Medicine Cheongju Korea

Aim:To investigate the ultrastructural localization of atrial natriuretic peptide(ANP)-synthesizing cells and the relationship between ANP-synthesizing cellsand microvessels in rat gastric mucosa.Methods:Immunohistochemistry tech-niques and postembedding immunoelectron microscopy techniques were used tovalidate the findings regarding the expression of ANP-synthesizing cells and theultrastructural localization of ANP-synthesizing cells in the gastric mucosa.His-tochemistry techniques and the tannic acid-ferric chloride method(TA-Fe stain-ing method)were used to reveal microvessel density and the distribution of ANP-synthesizing cells in different regions of the stomach.Results:Cells expressingANP were localized and ANP-synthesizing cells were identified as enterochroma-ffin(EC)cells in the gastric mucosa.ANP-synthesizing cells existed in differentregions of the stomach.The percentage ANP-synthesizing cells in the mucosawas greatest in the fundus(46.7%e5.3%),intermediate in the antrum(40.1%±4.5%),and least in the body(21.6%±3.6%).There was a positive relationshipbetween the percentage of ANP-synthesizing cells and the density of microvesselsin the antral mucosa,but not in the fundus or body mucosa.Conclusion:ANP issynthesized by EC cells in rat gastric mucosa,and ANP-synthesizing cells aremost dense in the gastric fundus.ANP may act not only as a regional autocrineand/or paracrine regulator,but also as an endocrine regulatory peptide in thegastrointestinal tract.

关键词： atrial natriuretic factor enterochromaffin cells blood vessels gastric mucosa

Evaluation of sensory function and recovery after replantation of fingertips at ZoneⅠin children

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Neural Regeneration Research 2017年第11期12卷 1911-1917页

作者： Zhao-wei Zhu Xiao-yan Zou Yong-jun Huang Jiang-hui Liu Xi-jun Huang Bo He Zeng-tao Wang Department of Plastic Surgery the First Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong ProvinceChina Department of Orthopedics and Microsurgery the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics Guangdong Second Provincial General HospitalGuangzhouGuangdong ProvinceChina Department of Emergency the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Hand and Foot Surgery Provincial Hospital Affiliated to Shandong UniversitylinanShandong ProvinceChina

Sensory function is the most significant criterion when evaluating the prognosis of replanted fingers. Current clinical research has focused on surgical techniques and indications for finger replantation; however, few studies have focused on recovery of finger sensory function af- ter replantation. This study retrospectively assessed data of eight patients who had undergone nine Zone I replantations of the fingertips in the First Affiliated Hospital of Sun Yat-sen University of China from July 2014 to January 2016. Variations in the extent of damage, with the residual vessels or nerves in some fingers being too short or even missing, prevented tension-free suture repair in some patients. Thus, re- pair of four of the nine fingertips included arteriovenous anastomosis, the remaining five undergoing arterial anastomosis during replanta- tion of the amputated fingers. Three patients underwent nerve repair, whereas the remaining six cases did not. Fingertip replantations were successful in all eight patients. Compared with the patients without vascular anastomosis, no obvious atrophy was visible in the fingertips of patients who did undergo vascular anastomosis during replantation and their sensory function did recover. Fingertip replantation pro- vides good sensory function and cosmetic outcomes when good artery and vein anastomoses have been created, even when digital nerves have not been repaired.

关键词： nerve regeneration fingertip replantation neurological function microsurgery hand surgery anatomy plastic surgery blood vessels neural regeneration

A free-breathing non-contrast-enhanced pulmonary magnetic resonance angiography at 3 Tesla

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Chinese Medical Journal 2009年第18期122卷 2111-2116页

作者： YANG Jian WANG Wei WANG Ya-rong NIU Gang JIN Chen-wang WU Ed Xuekui Medical Imaging Center First Hospital School of Medicine Xi'an Jiaotong University Xi'an Shaanxi 710061 China Department of Electrical and Electronic Engineering The University of Hong Kong Hong Kong SAR China Department of Diagnostic Radiology Tangdu Hospital Fourth Military Medical University Xi'an Shaanxi 710038 China School of Medicine Xi'an Jiaotong University Xi'an Shaanxi 710061 China

Background The breathhold contrast-enhanced three-dimensional magnetic resonance angiography （MRA） using Tl-weighted gradient-echo imaging sequence is the standard technique for MRA of the thorax. However, this technique is not desirable for certain patients with respiratory insufficiency, serious renal impairment, or allergy to contrast agents. The objective of this study was to optimize and evaluate a non-contrast-enhanced free-breathing pulmonary MRA protocol at 3 Tesla. Methods The time-of-flight protocol was based on a two-dimensional Tl-weighted turbo field echo sequence with slice-selective inversion recovery and magnetization transfer preparation together with respiratory navigator gating, cardiac gating, and parallel imaging. Optimal values for time of inversion delay, flip angle and slice thickness were experimentally determined and used for all subjects. Results Excellent pulmonary MRA images, in which the 7th order branches of pulmonary arteries could be reliably identified, were obtained in the 12 free-breathing healthy volunteers. TI of -300 ms provides the best suppression of background thoracic and cardiac muscles and effective inflow enhancement. With increasing flip angle, the pulmonary vessels gradually brightened and exhibited optimal contrast at 20°-30°. The 2 mm slice thickness and 0.5 mm slice overlap is suitable for visualization of the peripheral pulmonary vessel. Conclusions The MRA protocol at 3 Tesla may have clinical significance for pulmonary vascular imaging in patients who are not available for contrast-enhanced 3D MRA and CT angiography examination or are unable to sustain a long breath-hold.

关键词： magnetic resonance angiography pulmonary blood vessels

Decellularized aorta of fetal pigs as a potential scaffold for small diameter tissue engineered vascular graft

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Chinese Medical Journal 2008年第15期121卷 1398-1406页

作者： LIU Guo-feng HE Zhi-juan YANG Da-ping HAN Xue-feng GUO Tie-fang HAO Chen-guang MA Hui NIE Chun-lei Department of Plastic Surgery Second Affiliated Hospital of Harbin Medical University Harbin Heilongjiang 150086 China Department of Obstetrics and Gynecology First Affiliated Hospital of Harbin Medical University Harbin Heilongjiang 150010 China Department of Plastic Surgery Beijing Chaoyang Hospital Beijing 100020 China Department of Orthopaedics Heilongjiang Provincial Hospital Harbin Heilongjiang 150036 China

Background For cardiovascular tissue engineering, acellularized biomaterials from pig have been widely investigated. Our purpose was to study mechanical properties and biocompatibility of decellularized aorta of fetal pigs （DAFP） to determine its potential as scaffold for small diameter tissue engineered vascular graft. Methods Descending aorta of fetal pigs was removed cells using trypsin, ribonuclease and desoxyribonuclease. Mechanical properties of DAFP were evaluated by tensile stress-strain and burst pressure analysis. Assessment of cell adhesion and compatibility was conducted by seeding porcine aortic endothelial cells. To evaluate biocompatibility in vivo DAFP was implanted subcutaneously into adult male Sprague Dawley rats for 2, 4 and 8 weeks. Results Histochemistry and scanning electron microscopy examination of DAFP revealed well-preserved extracellular matrix proteins and porous three-dimensional structures. Compared with fresh aorta, DAFP had similar ultimate tensile strength, axial compliance and burst pressure. Cell culture studies in vitro showed that porcine aortic endothelial cells adhered and proliferated on the surfaces of DAFP with excellent cell viability. Subdermal implantation demonstrated that the DAFP did not show almost any immunological reaction and exhibited minimal calcification during the whole follow-up period. Conclusion The DAFP has the potential to serve as scaffolds for small diameter tissue engineered vascular graft.

关键词： tissue engineering blood vessels extracellular matrix calcium

The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells

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Neural Regeneration Research 2014年第10期9卷 1047-1054页

作者： Huanling Yao Tianshi Wang Jiexin Deng Ding Liu Xiaofei Li Jinbo Deng Institute of Neurobiology College of Life ScienceHenan University

Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.

关键词： nerve regeneration retina growth development blood vessels blood-retinal barrier astrocytes immunofluorescence ultrastructure mouse collagen IV glial fibrillary acidic protein NSFC grant neural regeneration

Human vascular smooth muscle cells and endothelial cells cocultured on polyglycolic acid (70/30) scaffold in tissue engineered vascular graft

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Chinese Medical Journal 2007年第15期120卷 1331-1335页

作者： WEN Shao-jun ZHAO Li-min WANG Shen-guo LI Jing-xing CHEN Hua-ying LIU Jie-lin LIU Ya LUO Yi Roo Changizi Central Experiment Unit Beijing Anzhen Hospital Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing 100029 China State Key Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing 100080 China Shunyi Clinic Beijing United Family Hospital Beijing 101300

Background Current prosthetic, small diameter vascular grafts showing poor long term patency rates have led to the pursuit of other biological materials. Biomaterials that successfully integrate into surrounding tissue should match not only the mechanical properties of tissues, but also topography. Polyglycolic acid （70130） has been used as synthetic grafts to determine whether human vascular smooth muscle cells and endothelial cells attach, survive and secrete endothelin and 6-keto-prostaglandin F1α （6-keto-PGF1α）. Methods Endothelial cells and smooth muscle cells were isolated from adult human great saphenous vein. They were seeded on polyglycolic acid scaffold in vitro separately to grew vascular patch （Groups A and B respectively） and cocultured in vitro to grow into vascular patch （Group C）. Smooth muscle cells and endothelial cells were identified by immunohistochemical analysis and growth of cells on polyglycolic acid was investigated using scanning electron microscopy. The levels of endothelin and 6-keto-PGF1α in the culturing solutions were examined by radioimmunology to measure endothelial function. Results Seed smooth muscle cells adhered to polyglycolic acid scaffold and over 28 days grew in the interstices to form a uniform cell distribution throughout the scaffold. Then seed endothelial cells formed a complete endothelial layer on the smooth muscle cells. The levels of endothelin and 6-keto-prostaglandin F1 alpha in the culturing solution were （234±29） pg/ml and （428±98） pg/ml respectively in Group C and （196±30） pg/ml and （346±120） pg/ml in Group B; both significantly higher than in Groups A and D （blank control group, all P〈0.05 ）. Conclusions Cells could be grown successfully on polyglycolic acid and retain functions of secretion. Our next step is to use human saphenous vein smooth muscle cells and endothelial cells to grow tubular vascular grafts in vitro.

关键词： tissue engineering blood vessels endothelial cells smooth muscle cells saphenous vein