|
|
Pharmacy Information 2024
血管内皮屏障功能损伤在疾病中的研究进展
|
Abstract:
许多疾病都具有血管渗漏的共同特征，内皮屏障功能损伤通常是其根本原因。内皮屏障是内皮细胞在血管腔和血管壁之间形成的独特屏障，具有选择性透过作用，对维持血管、组织和器官间的稳态至关重要。血管渗漏是由内皮细胞之间的间隙以及跨细胞转运途径的改变引起的。改善内皮屏障功能的具体机制取决于受影响的组织和引起高通透性的原因。本文综述了以内皮屏障破坏为特征的疾病，重点讨论了内皮屏障功能在急性肺损伤、缺血性脑卒中以及糖尿病并发症中的作用机制及其药物干预进展。
Many diseases have the common characteristics of vascular leakage, and the damage of endothelial barrier is the basic cause. The endothelial barrier is a unique barrier formed by endothelial cells between the vascular lumen and vascular wall. It has selective penetration and is essential for maintaining homeostasis among blood vessels, tissues, and organs. Vascular leakage is caused by changes in the spaces between endothelial cells and trans-cellular transport pathways. The mechanism for improving endothelial barrier function depends specifically on the affected tissue and the cause of the high permeability. This article reviews the diseases characterized by endothelial barrier disruption and discusses the mechanism of endothelial barrier function in acute lung injury, ischemic stroke, and diabetic complications and the progress of drug intervention.
| [1] | Claesson-Welsh, L., Dejana, E. and McDonald, D.M. (2021) Permeability of the Endothelial Barrier: Identifying and Reconciling Controversies. Trends in Molecular Medicine, 27, 314-331. https://doi.org/10.1016/j.molmed.2020.11.006 |
| [2] | Wu, Y., Yu, X., Wang, Y., et al. (2022) Ruscogenin Alleviates LPS-Triggered Pulmonary Endothelial Barrier Dysfunction through Targeting NMMHC IIA to Modulate TLR4 Signaling. Acta Pharmaceutica Sinica B, 12, 1198-1212. https://doi.org/10.1016/j.apsb.2021.09.017 |
| [3] | Nian, K., Harding, I.C., Herman, I.M., et al. (2020) Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction. Frontiers in Physiology, 11, Article 605398. https://doi.org/10.3389/fphys.2020.605398 |
| [4] | Hellenthal, K.E.M., Brabenec, L. and Wagner, N.M. (2022) Regulation and Dysregulation of Endothelial Permeability during Systemic Inflammation. Cells, 11, Article 1935. https://doi.org/10.3390/cells11121935 |
| [5] | Garcia-Flores, A.E., Gross, C.M., Zemskov, E.A., et al. (2022) Loss of SOX18/CLAUDIN5 Disrupts the Pulmonary Endothelial Barrier in Ventilator-Induced Lung Injury. Frontiers in Physiology, 13, Article 1066515. https://doi.org/10.3389/fphys.2022.1066515 |
| [6] | Zhang, J., Zhang, J., Zhang, C., et al. (2022) Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications. Cells, 11, Article 3362. https://doi.org/10.3390/cells11213362 |
| [7] | Colunga Biancatelli, R.M.L., Solopov, P., Gregory, B., et al. (2021) The HSP90 Inhibitor, AUY-922, Protects and Repairs Human Lung Microvascular Endothelial Cells from Hydrochloric Acid-Induced Endothelial Barrier Dysfunction. Cells, 10, Article 1489. https://doi.org/10.3390/cells10061489 |
| [8] | González-López, A. and Albaiceta, G.M. (2012) Repair after Acute Lung Injury: Molecular Mechanisms and Therapeutic Opportunities. Critical Care, 16, Article No. 209. https://doi.org/10.1186/cc11224 |
| [9] | Matthay, M.A. and Zemans, R.L. (2011) The Acute Respiratory Distress Syndrome: Pathogenesis and Treatment. Mechanisms of Disease, 6, 147-163. https://doi.org/10.1146/annurev-pathol-011110-130158 |
| [10] | Hao, Y., Wang, Z., Frimpong, F., et al. (2022) Calcium-Permeable Channels and Endothelial Dysfunction in Acute Lung Injury. Current Issues in Molecular Biology, 44, 2217-2229. https://doi.org/10.3390/cimb44050150 |
| [11] | Sukriti, S., Tauseef, M., Yazbeck, P., et al. (2014) Mechanisms Regulating Endothelial Permeability. Pulmonary Circulation, 4, 535-551. https://doi.org/10.1086/677356 |
| [12] | Silva, J.D., Su, Y., Calfee, C.S., et al. (2021) Mesenchymal Stromal Cell Extracellular Vesicles Rescue Mitochondrial Dysfunction and Improve Barrier Integrity in Clinically Relevant Models of ARDS. European Respiratory Journal, 58, Article 2002978. https://doi.org/10.1183/13993003.02978-2020 |
| [13] | Kong, X., Lin, D., Lu, L., et al. (2021) Apelin-13-Mediated AMPK Ameliorates Endothelial Barrier Dysfunction in Acute Lung Injury Mice via Improvement of Mitochondrial Function and Autophagy. International Immunopharmacol, 101, Article 108230. https://doi.org/10.1016/j.intimp.2021.108230 |
| [14] | Song, L., Shi, X., Kovacs, L., et al. (2023) Calpain Promotes LPS-Induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin. American Journal of Respiratory Cell and Molecular Biology, 69, 678-688. https://doi.org/10.1165/rcmb.2023-0009OC |
| [15] | Zhang, J.Z., Pan, Z.Q., Zhou, J.H., et al. (2022) The Myosin II Inhibitor, Blebbistatin, Ameliorates Pulmonary Endothelial Barrier Dysfunction in Acute Lung Injury Induced by LPS via NMMHC IIA/Wnt5a/β-Catenin Pathway. Toxicology and Applied Pharmacology, 450, Article 116132. https://doi.org/10.1016/j.taap.2022.116132 |
| [16] | Cong, X. and Kong, W. (2020) Endothelial Tight Junctions and Their Regulatory Signaling Pathways in Vascular Homeostasis and Disease. Cell Signal, 66, Article 109485. https://doi.org/10.1016/j.cellsig.2019.109485 |
| [17] | Han, D., Sun, J.J., Fan, D.K., et al. (2020) Simvastatin Ameliorates Oxygen Glucose Deprivation/Reoxygenation-Induced Pulmonary Endothelial Barrier Dysfunction by Restoring Cell-Cell Junctions and Actin cytoskeleton Dynamics via the PI3K/Akt Signaling Pathway. American Journal of Translational Research, 12, 5586-5596. |
| [18] | Xia, J.Y., Li, J.H., Deng, M.S., et al. (2023) Diosmetin Alleviates Acute Lung Injury Caused by Lipopolysaccharide by Targeting Barrier Function. Inflammopharmacology, 31, 2037-2047. https://doi.org/10.1007/s10787-023-01228-7 |
| [19] | Qi, D., Deng, W., Chen, X., et al. (2022) Adipose-Derived Circulating Exosomes Promote Protection of the Pulmonary Endothelial Barrier by Inhibiting EndMT and Oxidative Stress through Down-Regulation of the TGF-β Pathway: A Potential Explanation for the Obesity Paradox in ARDS. Oxidative Medicine and Cellular Longevity, 2022, Article ID: 5475832. https://doi.org/10.1155/2022/5475832 |
| [20] | Greene, C., Hanley, N. and Campbell, M. (2019) Claudin-5: Gatekeeper of Neurological Function. Fluids and Barriers of the CNS, 16, Article No. 3. https://doi.org/10.1186/s12987-019-0123-z |
| [21] | Abdullahi, W., Tripathi, D. and Ronaldson, P.T. (2018) Blood-Brain Barrier Dysfunction in Ischemic Stroke: Targeting Tight Junctions and Transporters for Vascular Protection. American Journal of Physiology-Cell Physiology, 315, C343-C356. https://doi.org/10.1152/ajpcell.00095.2018 |
| [22] | Gao, H.M., Chen, H., Cui, G.Y., et al. (2023) Damage Mechanism and Therapy Progress of the Blood-Brain Barrier after Ischemic Stroke. Cell and Bioscience, 13, Article No. 196. https://doi.org/10.1186/s13578-023-01126-z |
| [23] | Wang, J.H., Zhong, W., Cheng, Q.W., et al. (2022) Histone Methyltransferase Smyd2 Contributes to Blood-Brain Barrier Breakdown in Stroke. Clinical and Translational Medicine, 12, e761. https://doi.org/10.1002/ctm2.761 |
| [24] | Liberale, L., Gaul, D.S., Akhmedov, A., et al. (2020) Endothelial SIRT6 Blunts Stroke Size and Neurological Deficit by Preserving Blood-Brain Barrier Integrity: A Translational Study. European Heart Journal, 41, 1575-1587. https://doi.org/10.1093/eurheartj/ehz712 |
| [25] | Spellicy, S.E. and Hess, D.C. (2022) Recycled Translation: Repurposing Drugs for Stroke. Translational Stroke Research, 13, 866-880. https://doi.org/10.1007/s12975-022-01000-z |
| [26] | Huang, Y., Zhang, X., Zhang, C., et al. (2022) Edaravone Dexborneol Downregulates Neutrophil Extracellular Trap Expression and Ameliorates Blood-Brain Barrier Permeability in Acute Ischemic Stroke. Mediators of Inflammation, 2022, Article ID: 3855698. https://doi.org/10.1155/2022/3855698 |
| [27] | Xu, X.P., Zhou, R.X., Ying, J.J., et al. (2023) Irisin Prevents Hypoxic-Ischemic Brain Damage in Rats by Inhibiting Oxidative Stress and Protecting the Blood-Brain Barrier. Peptides, 161, Article 170945. https://doi.org/10.1016/j.peptides.2023.170945 |
| [28] | Wang, X., Yu, Z.Q., Dong, F.X., et al. (2023) Clarifying the Mechanism of Apigenin against Blood-Brain Barrier Disrupttion in Ischemic Stroke Using Systems Pharmacology. Molecular Diversity, 1-22. https://doi.org/10.1007/s11030-023-10607-9 |
| [29] | Yang, R., Shen, Y.J., Chen, M., et al. (2022) Quercetin Attenuates Ischemia Reperfusion Injury by Protecting the Blood-Brain Barrier through Sirt1 in MCAO Rats. Journal of Asian Natural Products Research, 24, 278-289. https://doi.org/10.1080/10286020.2021.1949302 |
| [30] | Robles-Osorio, M.L. and Sabath, E. (2023) Tight Junction Disruption and the Pathogenesis of the Chronic Complications of Diabetes Mellitus: A Narrative Review. World Journal of Diabetes, 14, 1013-1026. https://doi.org/10.4239/wjd.v14.i7.1013 |
| [31] | Rudraraju, M., Narayanan, S.P. and Somanath, P.R. (2020) Regulation of Blood-Retinal Barrier Cell-Junctions in Diabetic Retinopathy. Pharmacological Research, 161, 105-115. https://doi.org/10.1016/j.phrs.2020.105115 |
| [32] | Huang, C.Y., Zhou, T., Li, G., et al. (2019) Asymmetric Dimethylarginine Aggravates Blood-Retinal Barrier Breakdown of Diabetic Retinopathy via Inhibition of Intercellular Communication in Retinal Pericytes. Amino Acids, 51, 1515-1526. https://doi.org/10.1007/s00726-019-02788-1 |
| [33] | Li, J., Xie, R., Jiang, F., et al. (2021) Tumor Necrosis Factor Ligand-Related Molecule 1A Maintains Blood-Retinal Barrier via Modulating SHP-1-Src-VE-Cadherin Signaling in Diabetic Retinopathy. The FASEB Journal, 35, e22008. https://doi.org/10.1096/fj.202100807RR |
| [34] | Mohammad, G., Abdelaziz, G.M., Siddiquei, M.M., et al. (2019) Cross-Talk between Sirtuin 1 and the Proinflammatory Mediator High-Mobility Group Box-1 in the Regulation of Blood-Retinal Barrier Breakdown in Diabetic Retinopathy. Current Eye Research, 44, 1133-1143. https://doi.org/10.1080/02713683.2019.1625406 |
| [35] | Monickaraj, F., Acosta, G., Cabrera, A.P., et al. (2023) Transcriptomic Profiling Reveals Chemokine CXCL1 as a Mediator for Neutrophil Recruitment Associated with Blood-Retinal Barrier Alteration in Diabetic Retinopathy. Diabetes, 72, 781-794. https://doi.org/10.2337/db22-0619 |
| [36] | Samsu, N. (2021) Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Research International, 2021, Article ID: 1497449. https://doi.org/10.1155/2021/1497449 |
| [37] | Fatmi, A., Saadi, W., Beltrán-García, J., et al. (2022) The Endothelial Glycocalyx and Neonatal Sepsis. International Journal of Molecular Sciences, 24, Article 364. https://doi.org/10.3390/ijms24010364 |
| [38] | Crompton, M., Ferguson, J.K., Ramnath, R.D., et al. (2023) Mineralocorticoid Receptor Antagonism in Diabetes Reduces Albuminuria by Preserving the Glomerular Endothelial Glycocalyx. JCI Insight, 8, 154-164. https://doi.org/10.1172/jci.insight.154164 |
| [39] | Finch, N.C., Fawaz, S.S., Neal, C.R., et al. (2022) Reduced Glomerular Filtration in Diabetes Is Attributable to Loss of Density and Increased Resistance of Glomerular Endothelial Cell Fenestrations. Journal of the American Society of Nephrology, 33, 1120-1136. https://doi.org/10.1681/ASN.2021030294 |
| [40] | Richner, M., Ferreira, N., Dudele, A., et al. (2019) Functional and Structural Changes of the Blood-Nerve-Barrier in Diabetic Neuropathy. Frontiers in Neuroscience, 12, Article 1038. https://doi.org/10.3389/fnins.2018.01038 |
| [41] | Galiero, R., Caturano, A., Vetrano, E., et al. (2023) Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options. International Journal of Molecular Sciences, 24, Article 3554. https://doi.org/10.3390/ijms24043554 |
| [42] | Ben-Kraiem, A., Sauer, R.S., Norwig, C., et al. (2021) Selective Blood-Nerve Barrier Leakiness with Claudin-1 and Vessel-Associated Macrophage Loss in Diabetic Polyneuropathy. Journal of Molecular Medicine, 99, 1237-1250. https://doi.org/10.1007/s00109-021-02091-1 |
| [43] | Chapouly, C., Yao, Q., Vandierdonck, S., et al. (2016) Impaired Hedgehog Signalling-Induced Endothelial Dysfunction Is Sufficient to Induce Neuropathy: Implication in Diabetes. Cardiovascular Research, 109, 217-227. https://doi.org/10.1093/cvr/cvv263 |
| [44] | Konigs, V., Pierre, S., Schicht, M., et al. (2022) GPR40 Activation Abolishes Diabetes-Induced Painful Neuropathy by Suppressing VEGF-A Expression. Diabetes, 71, 774-787. https://doi.org/10.2337/db21-0711 |
| [45] | Szrejder, M., Rachubik, P., Rogacka, D., et al. (2020) Metformin Reduces TRPC6 Expression through AMPK Activation and Modulates Cytoskeleton Dynamics in Podocytes under Diabetic Conditions. Biochimica et Biophysica Acta—Molecular Basis of Disease, 1866, Article 165610. https://doi.org/10.1016/j.bbadis.2019.165610 |
| [46] | Haydinger, C.D., Ferreira, L.B., Williams, K.A., et al. (2023) Mechanisms of Macular Edema. Frontiers in Medicine, 10, Article 1128811. https://doi.org/10.3389/fmed.2023.1128811 |
| [47] | Zhao, T., Li, M., Xiang, Q., et al. (2022) Yishen Huashi Granules Ameliorated the Development of Diabetic Nephropathy by Reducing the Damage of Glomerular Filtration Barrier. Frontiers in Pharmacology, 13, Article 872940. https://doi.org/10.3389/fphar.2022.872940 |
| [48] | Sivakumar, P.M., Prabhakar, P.K., Cetinel, S., et al. (2022) Molecular Insights on the Therapeutic Effect of Selected Flavonoids on Diabetic Neuropathy. Mini-Reviews in Medicinal Chemistry, 22, 1828-1846. https://doi.org/10.2174/1389557522666220309140855 |
