Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction

Ranjan, Prabhat; Kumari, Rajesh; Goswami, Sumanta; Li, Jing; Pal, Harish C.; Suleiman, Zainab; Cheng, Zhongjian; Krishnamurthy, Prasanna; Kishore, Raj; Verma, Suresh

doi:10.3389/fcvm.2021.676267

Cited by 34 publications

(33 citation statements)

References 52 publications

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“…However, first in vitro approaches revealed that fibroblast not only secrete paracrine factors, but also release microRNA‐loaded exosomes to communicate with endothelial cells. In a profibrotic setting, it was shown that mouse cardiac endothelial cell function is impaired when cultured with exosomes that were isolated from TGFβ‐pretreated fibroblasts [122]. These findings are of potential interest since the up‐take of fibroblast‐derived miR in endothelial cells might change their phenotype toward mesenchymal cells.…”

Section: Communication Between Fibroblasts and Endothelial Cellsmentioning

confidence: 99%

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

et al. 2021

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Cardiac fibroblasts constitute a major cell population in the heart. They secrete extracellular matrix components and various other factors shaping the microenvironment of the heart. In silico analysis of intercellular communication based on single‐cell RNA sequencing revealed that fibroblasts are the source of the majority of outgoing signals to other cell types. This observation suggests that fibroblasts play key roles in orchestrating cellular interactions that maintain organ homeostasis but that can also contribute to disease states. Here, we will review the current knowledge of fibroblast interactions in the healthy, diseased, and aging heart. We focus on the interactions that fibroblasts establish with other cells of the heart, specifically cardiomyocytes, endothelial cells and immune cells, and particularly those relying on paracrine, electrical, and exosomal communication modes.

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Section: Communication Between Fibroblasts and Endothelial Cellsmentioning

confidence: 99%

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

et al. 2021

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“…As EVs play role in cardioprotective mechanisms [ 27 ], we expected that HeC modulate the release of mEVs by NRCFs. Here, we found that HeC tended to decrease the number of mEVs released by NRCFs, the cardioprotective role of which could be explained by a recent study which shown that EVs secreted by activated CFs impaired endothelial functions [ 39 ].…”

Section: Discussionmentioning

confidence: 89%

Helium Conditioning Increases Cardiac Fibroblast Migration Which Effect Is Not Propagated via Soluble Factors or Extracellular Vesicles

Jelemenský

Kovácsházi

Ferenczyová

et al. 2021

IJMS

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Helium inhalation induces cardioprotection against ischemia/reperfusion injury, the cellular mechanism of which remains not fully elucidated. Extracellular vesicles (EVs) are cell-derived, nano-sized membrane vesicles which play a role in cardioprotective mechanisms, but their function in helium conditioning (HeC) has not been studied so far. We hypothesized that HeC induces fibroblast-mediated cardioprotection via EVs. We isolated neonatal rat cardiac fibroblasts (NRCFs) and exposed them to glucose deprivation and HeC rendered by four cycles of 95% helium + 5% CO2 for 1 h, followed by 1 h under normoxic condition. After 40 h of HeC, NRCF activation was analyzed with a Western blot (WB) and migration assay. From the cell supernatant, medium extracellular vesicles (mEVs) were isolated with differential centrifugation and analyzed with WB and nanoparticle tracking analysis. The supernatant from HeC-treated NRCFs was transferred to naïve NRCFs or immortalized human umbilical vein endothelial cells (HUVEC-TERT2), and a migration and angiogenesis assay was performed. We found that HeC accelerated the migration of NRCFs and did not increase the expression of fibroblast activation markers. HeC tended to decrease mEV secretion of NRCFs, but the supernatant of HeC or the control NRCFs did not accelerate the migration of naïve NRCFs or affect the angiogenic potential of HUVEC-TERT2. In conclusion, HeC may contribute to cardioprotection by increasing fibroblast migration but not by releasing protective mEVs or soluble factors from cardiac fibroblasts.

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“…According to NYHA classification, a study found that the more severe the HF, the higher the MMP-9 level [ 33 ]. VEGF is an important growth factor, which is involved in many processes of human growth and development, such as angiogenesis and osteogenesis, and plays an important role in maintaining vascular homeostasis and normal cardiac function [ 34 ]. The level of VEGFA can regulate the HIF-1/VEGFA signaling pathway and reverse hypoxia-induced myocardial injury by regulating the level of HMOX1 [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Mechanisms of Tinglizi against Chronic Heart Failure Determined by Network Pharmacology and Molecular Docking

Luo

Wang

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Tinglizi has been extensively used to treat chronic heart failure (CHF) in modern times, but the material basis and pharmacological mechanisms are still unclear. To explore the material basis and corresponding potential targets and to elucidate the mechanism of Tinglizi, network pharmacology and molecular docking methods were utilized. Methods. The main chemical compounds and potential targets of Tinglizi were collected from the pharmacological database analysis platform (TCMSP). The corresponding genes of related action targets were queried through gene cards and UniProt database. The corresponding genes of CHF-related targets were searched through Disgenet database, and the intersection targets were obtained by drawing Venn map with the target genes related to pharmacodynamic components. Then, drug targets and disease targets were intersected and put into STRING database to establish a protein interaction network. The “active ingredient-CHF target” network was constructed with Cytoscape 3.8.2. Finally, Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of intersection targets were analyzed using metascape. With the aid of SYBYL software, the key active ingredients and core targets were docked at molecular level, and the results were visualized by PyMOL software. Molecular docking was carried out to investigate interactions between active compounds and potential targets. Results. A total of 12 active components in Tinglizi were chosen from the TCMSP database, and 193 corresponding targets were predicted. Twenty-nine potential targets of Tinglizi on CHF were obtained, of which nine were the core targets of this study. Twenty GO items were obtained by GO function enrichment analysis ( P < 0.05 ), and 10 signal pathways were screened by KEGG pathway enrichment analysis ( P < 0.05 ), which is closely related to the treatment of CHF by Tinglizi. The constructed drug compound composition action target disease network shows that quercetin, kaempferol, and other active compounds play a key role in the whole network. The results of molecular docking showed that all the key active ingredients, such as quercetin and isorhamnetin, were able to successfully dock with ADRB2 and HMOX1 with a total score above 5.0, suggesting that these key components have a strong binding force with the targets. Conclusion. Through network pharmacology and molecular docking technology, we found that the main components of Tinglizi in the treatment of CHF are quercetin, kaempferol, β-sitosterol, isorhamnetin, and so on. The action targets are beta 2-adrenergic receptor (ADRB2), heme oxygenase 1 (HMOX1), and so on. The main pathways are advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, hypoxia-inducible factor (HIF-1) signaling pathway, estrogen signaling pathway, and so on. They play an integrated role in the treatment of CHF.

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Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction

Cited by 34 publications

References 52 publications

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

Fibroblast‐mediated intercellular crosstalk in the healthy and diseased heart

Helium Conditioning Increases Cardiac Fibroblast Migration Which Effect Is Not Propagated via Soluble Factors or Extracellular Vesicles

Pharmacological Mechanisms of Tinglizi against Chronic Heart Failure Determined by Network Pharmacology and Molecular Docking

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