Distinct patterns of responses in endothelial cells and smooth muscle cells following vascular injury

Ding, Xia; An, Qi; Wang, Zhao; Song, Yang; Tang, Xiaokai; Wang, Jing; Chang, Chih-Chiang; Zhao, Gexin; Hsiai, Tzung K.; Fan, Guoping; Fan, Yubo; Li, Song

doi:10.1172/jci.insight.153769

Cited by 7 publications

(7 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…What is more, AngII is an inducer of VCAM-1 expression in VSMCs [31]. In a vascular injury model, single-cell RNA-seq analysis showed that the inflammatory cells mainly cross-talked with smooth muscle cells rather than other cells including endothelial cells [32], which supported our results indicating that the upregulation of VCAM-1 expression in VSMCs plays an important role in vascular wall inflammation. Our data showed that CD38 SKO significantly reduced the AngII-induced increases in the expression of VCAM-1 and P65 acetylation which were eliminated by Ex527, a SIRT1 inhibitor.…”

Section: Discussionsupporting

confidence: 86%

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling

Yu,

Wang,

Wang

et al. 2024

IJMS

View full text Add to dashboard Cite

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe−/− mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.

show abstract

Section: Discussionsupporting

confidence: 86%

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling

Yu,

Wang,

Wang

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…ECs have been reported to express perivascular markers, such as αSMA (α-smooth muscle actin) and Tagln. [33][34][35][36][37][38] Thus, it was not surprising to find that some of these markers were coexpressed by SMC clusters (Figure S1B). An EC cluster expressed several genes specific to G2/M (Top2a, Mki67, Birc5, Cenpa, Kif2c, Bub1, Nuf2, and Hmmr; Ung, Chaf1b, Fen1, and Gmnn; Figure 1I; Figure S1G through S1J) transition.…”

Section: Increase In Cycling Neonatal Aecs Post-mimentioning

confidence: 91%

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice

Arolkar,

Kumar,

Wang

et al. 2023

ATVB

View full text Add to dashboard Cite

Background: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. Methods: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. Results: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. Conclusions: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

show abstract

“…LGMN has highly expressed in neovascularization endothelial cells in the tumor microenvironment. To study the effect of LGMN on the lumen formation of human venous endothelial cells (HUVEC), it was added APEI, an inhibitor of LGMN, into the medium ( Ding et al, 2022 ; Lu et al, 2022 ). The experimental results show that the number of intact tubules formed by HUVEC cells was significantly reduced and further decreased with the increase of APEI addition, suggesting that the high expression of LGMN in vascular endothelial cells of tumor tissue may promote the formation of tumor neovascularization, improve tumor blood supply, and promote tumor growth.…”

Section: Relationship Between Lgmn and Tumor Microenvironmentmentioning

confidence: 99%

Role of LGMN in tumor development and its progression and connection with the tumor microenvironment

Khan

Khan²,

Khan³

et al. 2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also in the macrophages that compose the tumor microenvironment. This supports the idea that LGMN is a pivotal protein in regulating tumor development, invasion, and dissemination. Targeting LGMN with siRNA or chemotherapeutic medicines and peptides can suppress cancer cell proliferation in culture and reduce tumor growth in vivo. Furthermore, legumain can be used as a marker for cancer detection and targeting due to its expression being significantly lower in normal cells compared to tumors or tumor-associated macrophages (TAMs). Tumor formation is influenced by aberrant expression of proteins and alterations in cellular architecture, but the tumor microenvironment is a crucial deciding factor. Legumain (LGMN) is an in vivo-active cysteine protease that catalyzes the degradation of numerous proteins. Its precise biological mechanism encompasses a number of routes, including effects on tumor-associated macrophage and neovascular endothelium in the tumor microenvironment. The purpose of this work is to establish a rationale for thoroughly investigating the function of LGMN in the tumor microenvironment and discovering novel tumor early diagnosis markers and therapeutic targets by reviewing the function of LGMN in tumor genesis and progression and its relationship with tumor milieu.

show abstract

Distinct patterns of responses in endothelial cells and smooth muscle cells following vascular injury

Cited by 7 publications

References 64 publications

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice

Role of LGMN in tumor development and its progression and connection with the tumor microenvironment

Contact Info

Product

Resources

About