Loss of Jagged1 in mature endothelial cells causes vascular dysfunction with alterations in smooth muscle phenotypes

Breikaa, Randa M.; Denman, Kimberly; Ueyama, Yukie; McCallinhart, Patricia E.; Khan, Aiman; Agarwal, Gunjan; Trask, Aaron J.; Garg, Vidu; Lilly, Brenda

doi:10.1016/j.vph.2022.107087

Cited by 16 publications

(10 citation statements)

References 41 publications

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“…The Jag-Notch signaling controls vascular development in embryonic and adult tissues. Specifically, Endothelial cell-derived Jag1 is essential for blood vessel formation by enhancing the differentiation and maturation of vascular smooth muscle cells[30, 31].…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of intercellular communication in thermogenic adipose niche

Shamsi

Zheng

et al. 2022

Preprint

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Brown adipose tissue (BAT) is responsible for regulating body temperature through adaptive thermogenesis. The ability of thermogenic adipocytes to dissipate chemical energy as heat counteracts weight gain and has gained considerable attention as a strategy against obesity. BAT undergoes major remodeling in a cold environment. This remodeling results from changes in the number and function of brown adipocytes, expanding the network of blood vessels and sympathetic nerves, and changes in the makeup and function of immune cells. All these processes are essential for enhanced BAT thermogenesis to maintain euthermia in the cold. Such synergistic adaptation requires extensive crosstalk between the individual cells in tissues to coordinate their responses. To understand the mechanisms of intercellular communication in BAT, we applied the CellChat algorithm to single-cell transcriptomic data of mouse BAT. We constructed an integrative network of ligand-receptor interactome in BAT and identified the major signaling input and output of each cell type. By comparing the ligand-receptor interactions in BAT of mice housed at different environmental temperatures, we found that cold exposure enhances the intercellular interactions among the major cell types in BAT, including adipocytes, adipocyte progenitors, lymphatic and vascular endothelial cells, myelinated Schwann cells (MSC), non-myelinated Schwann cells (NMSC), and immune cells. Furthermore, we identified the ligands and receptors that are regulated at the transcriptional level by temperature. These interactions are predicted to regulate the remodeling of extracellular matrix (ECM), inflammatory response, angiogenesis, and neurite growth. Together, our integrative analysis of intercellular communications in BAT and their dynamic regulation in response to housing temperatures establishes a holistic understanding of the mechanisms involved in BAT thermogenesis. The resources presented in this study provide a valuable platform for future investigations of BAT development and thermogenesis.

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Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of intercellular communication in thermogenic adipose niche

Shamsi

Zheng

et al. 2022

Preprint

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“…32 Adherence of ECs to smooth muscle cells is critical for maintaining vascular stability and integrity during angiogenesis. 33 The state of blood vessels is typically assessed by costaining the EC marker CD31 with the α-SMA marker, which represents mature smooth muscle cells, using immunofluorescence. 34 Wound neovascularisation provides nutrients for cell migration and promotes wound healing.…”

Section: Discussionmentioning

confidence: 99%

“…This neovascularisation provides metabolic support for tissue repair and hastens wound healing 32 . Adherence of ECs to smooth muscle cells is critical for maintaining vascular stability and integrity during angiogenesis 33 . The state of blood vessels is typically assessed by costaining the EC marker CD31 with the α‐SMA marker, which represents mature smooth muscle cells, using immunofluorescence 34 .…”

Section: Discussionmentioning

confidence: 99%

Fucoidan promotes angiogenesis and accelerates wound healing through AKT/Nrf2/HIF‐1α signalling pathway

Wen,

Yang,

Wang

et al. 2023

International Wound Journal

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After skin injury, wound repair involves a complex process in which angiogenesis plays a crucial role. Previous research has indicated that fucoidan may aid in wound healing; we therefore hypothesised that fucoidan may speed up the process by promoting angiogenesis. In this study, we investigated the potential molecular mechanism underlying fucoidan's ability to accelerate wound healing by promoting angiogenesis. Using a full‐cut wound model, we observed that fucoidan significantly intensified wound closure and promoted granulation formation and collagen deposition. Immunofluorescence staining revealed that fucoidan also promoted wound angiogenesis, specifically by accelerating the migration of new blood vessels to the middle area of the wound. Furthermore, fucoidan demonstrated the ability to enhance the proliferation of human umbilical vein endothelial cells (HUVECs) damaged by hydrogen peroxide (H2O2) and to improve the formation of endothelial tubes. Mechanistic studies revealed that fucoidan upregulated the protein levels of the AKT/Nrf2/HIF‐1α signalling pathway, which plays a crucial role in angiogenesis. This was further confirmed using the inhibitor LY294002, which reversed the promotion of endothelial tube formation by fucoidan. Overall, our findings suggest that fucoidan can promote angiogenesis via the AKT/Nrf2/HIF‐1α signalling pathway and accelerate wound healing.

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“…Many of the molecular pathways involved in endothelial dysfunction are well known, and include, together with the above cited players such as nitric oxide synthase (NO), lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) involved in the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway [ 60 , 61 ], emerging pathways such as those related to loss of function of the protein KRIT1 [ 62 ], and the epidermal growth factor receptor (EGFR) [ 43 ]. Recently, pathways known to regulate the development of the cardiovascular system, such as Notch [ 63 , 64 , 65 , 66 ], Hedgehog [ 67 ], and Wnt [ 68 ], have been identified as major determinant of the health of the endothelium and new pathways are being discovered [ 69 ].This knowledge will be crucial to identify novel therapeutic targets for patients that do not respond to commonly used treatments or become resistant to them and to identify bioactive molecules able to prevent/counteract endothelial dysfunction and related pathologies.…”

Section: Endothelial Dysfunction and Its Major Complicationsmentioning

confidence: 99%

Agri-Food Waste from Apple, Pear, and Sugar Beet as a Source of Protective Bioactive Molecules for Endothelial Dysfunction and Its Major Complications

et al. 2022

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Endothelial damage is recognized as the initial step that precedes several cardiovascular diseases (CVD), such as atherosclerosis, hypertension, and coronary artery disease. It has been demonstrated that the best treatment for CVD is prevention, and, in the frame of a healthy lifestyle, the consumption of vegetables, rich in bioactive molecules, appears effective at reducing the risk of CVD. In this context, the large amount of agri-food industry waste, considered a global problem due to its environmental and economic impact, represents an unexplored source of bioactive compounds. This review provides a summary regarding the possible exploitation of waste or by-products derived by the processing of three traditional Italian crops—apple, pear, and sugar beet—as a source of bioactive molecules to protect endothelial function. Particular attention has been given to the bioactive chemical profile of these pomaces and their efficacy in various pathological conditions related to endothelial dysfunction. The waste matrices of apple, pear, and sugar beet crops can represent promising starting material for producing “upcycled” products with functional applications, such as the prevention of endothelial dysfunction linked to cardiovascular diseases.

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Loss of Jagged1 in mature endothelial cells causes vascular dysfunction with alterations in smooth muscle phenotypes

Cited by 16 publications

References 41 publications

Comprehensive analysis of intercellular communication in thermogenic adipose niche

Comprehensive analysis of intercellular communication in thermogenic adipose niche

Fucoidan promotes angiogenesis and accelerates wound healing through AKT/Nrf2/HIF‐1α signalling pathway

Agri-Food Waste from Apple, Pear, and Sugar Beet as a Source of Protective Bioactive Molecules for Endothelial Dysfunction and Its Major Complications

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