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Citations to this article

Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation
Theresa Failer, … , Vladimir Todorov, Irakli Kopaliani
Theresa Failer, … , Vladimir Todorov, Irakli Kopaliani
Published February 8, 2022
Citation Information: J Clin Invest. 2022;132(6):e126155. https://doi.org/10.1172/JCI126155.
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Research Article Cardiology Inflammation Article has an altmetric score of 15

Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation

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Abstract

The causative role of inflammation in hypertension-related cardiovascular diseases is evident and calls for development of specific immunomodulatory therapies. We tested the therapeutic efficacy and mechanisms of action of developmental endothelial locus-1 (DEL-1), an endogenous antiinflammatory factor, in angiotensin II– (ANGII–) and deoxycorticosterone acetate–salt–induced (DOCA-salt–induced) cardiovascular organ damage and hypertension. By using mice with endothelial overexpression of DEL-1 (EC-Del1 mice) and performing preventive and interventional studies by injecting recombinant DEL-1 in mice, we showed that DEL-1 improved endothelial function and abrogated aortic adventitial fibrosis, medial thickening, and loss of elastin. DEL-1 also protected the mice from cardiac concentric hypertrophy and interstitial and perivascular coronary fibrosis and improved left ventricular function and myocardial coronary perfusion. DEL-1 prevented aortic stiffness and abolished the progression of hypertension. Mechanistically, DEL-1 acted by inhibiting αvβ3 integrin–dependent activation of pro-MMP2 in mice and in human isolated aorta. Moreover, DEL-1 stabilized αvβ3 integrin–dependent CD25+FoxP3+ Treg numbers and IL-10 levels, which were associated with decreased recruitment of inflammatory cells and reduced production of proinflammatory cytokines in cardiovascular organs. The demonstrated effects and immune-modulating mechanisms of DEL-1 in abrogation of cardiovascular remodeling and progression of hypertension identify DEL-1 as a potential therapeutic factor.

Authors

Theresa Failer, Michael Amponsah-Offeh, Aleš Neuwirth, Ioannis Kourtzelis, Pallavi Subramanian, Peter Mirtschink, Mirko Peitzsch, Klaus Matschke, Sems M. Tugtekin, Tetsuhiro Kajikawa, Xiaofei Li, Anne Steglich, Florian Gembardt, Annika C. Wegner, Christian Hugo, George Hajishengallis, Triantafyllos Chavakis, Andreas Deussen, Vladimir Todorov, Irakli Kopaliani

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Total citations by year

Year: 2025 2024 2023 2022 Total
Citations: 2 8 7 4 21
Citation information
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Citations to this article (21)

Title and authors Publication Year
Miglustat ameliorates isoproterenol-induced cardiac fibrosis via targeting UGCG
Liu J, Li W, Jiao R, Liu Z, Zhang T, Chai D, Meng L, Yang Z, Liu Y, Wu H, Gu X, Li X, Yang C
Molecular Medicine 2025
Molecular mechanisms and intervention approaches of heart failure (Review)
Guo S, Hu Y, Ling L, Yang Z, Wan L, Yang X, Lei M, Guo X, Ren Z
International Journal of Molecular Medicine 2025
Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets
Xia Y, Gao D, Wang X, Liu B, Shan X, Sun Y, Ma D
Frontiers in immunology 2024
Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.
Zhang S, Zhang Q, Lu Y, Chen J, Liu J, Li Z, Xie Z
International journal of molecular sciences 2024
Epidermal Growth Factor-Like Repeats and Discoidin I-Like Domains 3 Deficiency Attenuates Dilated Cardiomyopathy by Inhibiting Ubiquitin Specific Peptidase 10 Dependent Smad4 Deubiquitination.
Zhao M, Zheng Z, Peng S, Xu Y, Zhang J, Liu J, Pan W, Yin Z, Xu S, Wei C, Wang M, Wan J, Qin JJ
Journal of the American Heart Association 2024
Endothelial dysfunction: mechanisms and contribution to diseases.
Ajoolabady A, Pratico D, Ren J
Acta Pharmacologica Sinica 2024
Developmental endothelial locus 1: the present and future of an endogenous factor in vessels
Jiang D, Yue H, Liang WT, Wu Z
Frontiers in Physiology 2024
EDIL3/Del-1 prevents aortic dissection through enhancing internalization and degradation of apoptotic vascular smooth muscle cells
Yin Z, Zhang J, Zhao M, Liu J, Xu Y, Peng S, Pan W, Wei C, Zheng Z, Liu S, Qin JJ, Wan J, Wang M
Autophagy 2024
Bridging the Gap: Endothelial Dysfunction and the Role of iPSC-Derived Endothelial Cells in Disease Modeling
Sgromo C, Cucci A, Venturin G, Follenzi A, Olgasi C
International Journal of Molecular Sciences 2024
Immune and Metabolic Mechanisms of Endothelial Dysfunction
Kopaliani I, Elsaid B, Speier S, Deussen A
International Journal of Molecular Sciences 2024
Targeting regulatory T cells for cardiovascular diseases
Wang X, Zhou H, Liu Q, Cheng P, Zhao T, Yang T, Zhao Y, Sha W, Zhao Y, Qu H
Frontiers in immunology 2023
Deficiency of Tregs in hypertension‐associated left ventricular hypertrophy
Tang Y, Shen L, Bao J, Xu D
The Journal of Clinical Hypertension 2023
Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy
Romanidou G, Konstantinidis TG, Natsi AM, Kantartzi K, Panopoulou M, Kontomanolis E, Tsigalou C, Lambropoulou M, Gavriilaki E, Panagoutsos S, Pasadakis P, Mitroulis I
International journal of molecular sciences 2023
Regulatory T cells and cardiovascular diseases
Hu W, Li J, Cheng X
Chinese Medical Journal 2023
Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution
ZHU L, SUN Z, GUAN Y, LIU M, ZHENG Y, YU R, WANG Q, LI L
Journal of Traditional Chinese Medicine 2023
Decreased GCF DEL-1 and increased GCF neutrophils with increasing probing pocket depth.
Jin SH, Lee EM, Park JB, Ko Y
Journal of periodontal & implant science 2023
The Molecular Mechanism and Therapeutic Strategy of Cardiorenal Syndrome Type 3
Liu Y, Guan X, Shao Y, Zhou J, Huang Y
2023
Modulating the immune response to reduce hypertension-associated cardiovascular damages
Daniel Henrion
Journal of Clinical Investigation 2022
Commentary on "Failer et al. (2022) Developmental endothelial locus-1 protects from hypertension-induced cardiovascular remodeling via immunomodulation" J Clin Invest 2022 (https://doi.org/10.1172/JCI126155).
Sperandio M
2022
Developmental endothelial locus-1 in cardiovascular and metabolic diseases: A promising biomarker and therapeutic target
Zhao M, Zheng Z, Li C, Wan J, Wang M
Frontiers in immunology 2022
Targeting inflammation in hypertension
Deussen A, Kopaliani I
Current Opinion in Nephrology and Hypertension 2022

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