Differentially expressed lnc‐NOS2P3‐miR‐939‐5p axis in chronic heart failure inhibits myocardial and endothelial cells apoptosis via iNOS/TNFα pathway

et al. 2021

Bioengineered

Tumor-derived exosomes (exo) could modulate the biological behaviors of human umbilical vein endothelial cells (HUVECs). Here, the role of microRNA (miR)-10a-5p-modified gastric cancer (GC) cells-derived exo for HUVECs was studied. GC tissue specimens were collected, and miR-10a-5p and zinc finger MYND-type containing 11 (ZMYND11) levels were determined. HUVECs interfered with ZMYND11 or miR-10a-5p-related oligonucleotides. Exo was extracted from GC cells (HGC-27 exo), and miR-10a-5p mimic-modified HGC-27 exo were co-cultured with HUVECs. HUVECs viability, migration and angiogenesis were evaluated, and miR-10a-5p/ZMYND11 crosstalk was explored. It was observed that GC patients had raised miR-10a-5p and reduced ZMYND11, and miR-10a-5p negatively mediated ZMYND11 expression. Suppression of miR-10a-5p or overexpression of ZMYND11 inhibited viability, migration and tube formation ability of HUVECs. Notably, miR-10a-5p mimic-modified HGC-27 exo enhanced the viability, migration and tube formation ability of HUVECs, but this effect was impaired after up-regulating ZMYND11. In summary, miR-10a-5p from GC cells-derived exo enhances viability and migration of HUVECs by suppressing ZMYND11.

“…The media were provided by HyClone, Thermo Scientific (UT, USA). HUVECs (ATCC®CRL-1730™) were cultivated in 10% FBS-RPMI 1640 medium (GIBCO, NY, USA) [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: microRNA-10a-5p from gastric cancer cell-derived exosomes enhances viability and migration of human umbilical vein endothelial cells by targeting zinc finger MYND-type containing 11

Zhu

et al. 2021

Bioengineered

“…Excessive apoptosis of endothelial cells severely interferes with endothelial integrity and endothelial function, resulting in endothelial damage, which is closely associated with the occurrence and the development of various cardiovascular diseases [2][3][4][5][6]. NO, which is predominantly synthesized by eNOS in endothelial cells, is a vasoactive substance secreted by endothelial cells [7].…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial cell apoptosis triggers vascular endothelial injury [1] and is the pathophysiological basis of numerous cardiovascular diseases, including atherosclerosis, hypertension, aneurysm, and pulmonary hypertension [2][3][4][5][6]. In endothelial cells, nitric oxide (NO) predominantly synthesized by endothelial nitric oxide synthase (eNOS) has an anti-apoptotic effect, and therefore, it is a crucial vascular protective gasotransmitter [7].…”

mentioning

confidence: 99%

Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine‐dependent SOD1 monomerization

Peng

et al. 2022

FEBS Open Bio

Endothelial cell apoptosis is an important pathophysiology in many cardiovascular diseases. The gasotransmitter nitric oxide (NO) is known to regulate cell survival and apoptosis. However, the mechanism underlying the effect of NO remains unclear. In this research, by targeting cytosolic copper/zinc superoxide dismutase (SOD1) monomerization, we aimed to explore how NO inhibited endothelial cell apoptosis. We showed that treatment with the NO synthase (NOS) inhibitor nomega‐nitro‐l‐arginine methyl ester hydrochloride (L‐NAME) significantly decreased the endogenous NO content of endothelial cells, facilitated the formation of SOD1 monomers, inhibited dismutase activity, and promoted reactive oxygen species (ROS) accumulation in human umbilical vein endothelial cells (HUVECs); by contrast, supplementation with the NO donor sodium nitroprusside (SNP) upregulated NO content, prevented the formation of SOD1 monomers, enhanced dismutase activity, and reduced ROS accumulation in L‐NAME‐treated HUVECs. Mechanistically, tris(2‐carboxyethyl) phosphine hydrochloride (TCEP), a specific reducer of cysteine thiol, increased SOD1 monomer formation, thus preventing the NO‐induced increase in dismutase activity and the decrease in ROS. Furthermore, SNP inhibited HUVEC apoptosis caused by the decrease in endogenous NO, whereas TCEP abolished this protective effect of SNP. In summary, our data reveal that NO protects endothelial cells against apoptosis by inhibiting cysteine‐dependent SOD1 monomerization to enhance SOD1 activity and inhibit oxidative stress.

“…A previous study showed that restricting the TNF-α can inhibit the process of CHF, which may become a novel way to treat CHF (77). The excitation-contraction coupling of cardiomyocytes is closely related to calcium ion (Ca 2+ ) regulation.…”

Section: Discussionmentioning

confidence: 99%

Integration of network pharmacology and molecular docking technology reveals the mechanism of the herbal pairing of Codonopsis Pilosula (Franch.) Nannf and Astragalus Membranaceus (Fisch.) Bge on chronic heart failure

Zhou

et al. 2021

Ann Palliat Med

Background: The herbal pairing of Dangshen (DS) [Codonopsis pilosula (Franch.) Nannf.] and Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.] (DHP) is a traditional Chinese herbal medicine that is frequently used to treat chronic heart failure (CHF) in China. However, the pharmacological mechanism of DHP has not been fully elucidated. This is the first study aimed to reveal the active mechanism of DHP in the treatment of CHF by using network pharmacology methods. Methods:The active ingredients of DHP were obtained from the TCMSP database, and the potential targets of DHP were predicted using the SwissTargetPrediction database. CHF-related targets were searched by the DisGeNET and GeneCards databases. The common targets between the disease and herbs were obtained using a Venn diagram. The STRING database was utilized to obtain the protein-protein interaction data. Next, we used Cytoscape 3.7.2 software to construct and analyze the herb-ingredientpotential targets-disease network. Topology analysis was used to identify the key ingredients and hub genes.GO and KEGG pathway enrichment analyses were performed using the Metascape database to reveal the mechanism. Furthermore, molecular docking simulation was performed using AutoDock Vina software to assess the affinity of the key ingredients and hub genes.Results: Five key ingredients and six hub genes were screened. The six hub genes were closely related to PI3K /AKT or ERK1/2 pathways. The KEGG pathways mainly involved the TNF signaling pathway, calcium signaling pathway, and cancer-related pathways. The GO enrichment analysis results showed that DHP might act on biological processes including positive regulation of kinase activity and cellular response to nitrogen compound via the three above-mentioned pathways in the treatment of CHF. Finally, the molecular docking results showed that the five key ingredients exhibited strong affinities to the six hub genes.Conclusions: This study revealed the molecular mechanism that the flavonoids in DHP may alleviate endothelial dysfunction and cardiac hypertrophy via regulation of the TNF pathway and its downstream PI3K/Akt or ERK1/2 signaling pathways, or improve excitation-contraction coupling by regulating calcium ^ ORCID: Jianglin Xu,