Beraprost sodium attenuates cigarette smoke extract-induced apoptosis in vascular endothelial cells

Cigarette smoke-induced apoptosis of vascular endothelial cells contributes to the pathogenesis of chronic obstructive pulmonary disease. However, the mechanisms responsible for endothelial apoptosis remain poorly understood. We conducted an in vitro study to investigate whether DNA methylation is involved in smoking-induced endothelial apoptosis. Human umbilical vascular endothelial cells (HUVECs) were exposed to cigarette smoke extract (CSE) at a range of concentrations (0–10%). HUVECs were also incubated with a demethylating reagent, 5-aza-2′-deoxycytidinem (AZA), with and without CSE. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and flow cytometry using annexin V-FITC/propidium iodide staining. We found that CSE treatment significantly increased HUVEC apoptosis in a dose- and time-dependent manner. Quantitative real-time RT-PCR and immunoblot revealed that CSE treatment decreased cytochrome- c oxidase subunit II (COX II) mRNA and protein levels and decreased COX activity. Methylation-specific PCR and direct bisulfite sequencing revealed positive COX II gene methylation. AZA administration partly increased mRNA and protein expressions of COX II, and COX activity decreased by CSE and attenuated the toxic effects of CSE. Our results showed that CSE induced aberrant COX II methylation and apoptosis in HUVECs.

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Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells

Scientific Reports ◽

10.1038/s41598-021-85534-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ashish Saxena ◽

Matthew S. Walters ◽

Jae-Hung Shieh ◽

Ling-Bo Shen ◽

Kazunori Gomi ◽

...

Keyword(s):

Endothelial Cells ◽

Cigarette Smoke ◽

Extracellular Vesicles ◽

Basal Cell ◽

Mapk Signaling ◽

Cigarette Smoke Extract ◽

Vegf Receptor ◽

Vascular Endothelial ◽

Basal Cells ◽

Human Airway

AbstractThe human airway epithelium lining the bronchial tree contains basal cells that proliferate, differentiate, and communicate with other components of their microenvironment. One method that cells use for intercellular communication involves the secretion of exosomes and other extracellular vesicles (EVs). We isolated exosome-enriched EVs that were produced from an immortalized human airway basal cell line (BCi-NS1.1) and found that their secretion is increased by exposure to cigarette smoke extract, suggesting that this stress stimulates release of EVs which could affect signaling to other cells. We have previously shown that primary human airway basal cells secrete vascular endothelial growth factor A (VEGFA) which can activate MAPK signaling cascades in endothelial cells via VEGF receptor–2 (VEGFR2). Here, we show that exposure of endothelial cells to exosome-enriched airway basal cell EVs promotes the survival of these cells and that this effect also involves VEGFR2 activation and is, at least in part, mediated by VEGFA present in the EVs. These observations demonstrate that EVs are involved in the intercellular signaling between airway basal cells and the endothelium which we previously reported. The downstream signaling pathways involved may be distinct and specific to the EVs, however, as increased phosphorylation of Akt, STAT3, p44/42 MAPK, and p38 MAPK was not seen following exposure of endothelial cells to airway basal cell EVs.

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miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

Scientific Reports ◽

10.1038/s41598-021-95712-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jizhi Wu ◽

Guangqi Zhang ◽

Hui Xiong ◽

Yuguang Zhang ◽

Gang Ding ◽

...

Keyword(s):

Endothelial Cells ◽

Oxygen Therapy ◽

Vascular Endothelial Cells ◽

Inhibitory Effect ◽

Vascular Endothelial ◽

Pulmonary Capillaries ◽

Pulmonary Capillary ◽

Capillary Endothelial Cells ◽

Nasal Inhalation ◽

Induced Apoptosis

AbstractOxygen therapy has been widely used in clinical practice, especially in anesthesia and emergency medicine. However, the risks of hyperoxemia caused by excessive O2 supply have not been sufficiently appreciated. Because nasal inhalation is mostly used for oxygen therapy, the pulmonary capillaries are often the first to be damaged by hyperoxia, causing many serious consequences. Nevertheless, the molecular mechanism by which hyperoxia injures pulmonary capillary endothelial cells (LMECs) has not been fully elucidated. Therefore, we systematically investigated these issues using next-generation sequencing and functional research techniques by focusing on non-coding RNAs. Our results showed that hyperoxia significantly induced apoptosis and profoundly affected the transcriptome profiles of LMECs. Hyperoxia significantly up-regulated miR-181c-5p expression, while down-regulated the expressions of NCAPG and lncRNA-DLEU2 in LMECs. Moreover, LncRNA-DLEU2 could bind complementarily to miR-181c-5p and acted as a miRNA sponge to block the inhibitory effect of miR-181c-5p on its target gene NCAPG. The down-regulation of lncRNA-DLEU2 induced by hyperoxia abrogated its inhibition of miR-181c-5p function, which together with the hyperoxia-induced upregulation of miR-181c-5p, all these significantly decreased the expression of NCAPG, resulting in apoptosis of LMECs. Our results demonstrated a ceRNA network consisting of lncRNA-DLEU2, miR-181c-5p and NCAPG, which played an important role in hyperoxia-induced apoptosis of vascular endothelial injury. Our findings will contribute to the full understanding of the harmful effects of hyperoxia and to find ways for effectively mitigating its deleterious effects.

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