Background The role of microRNAs dysregulation in tobacco cigarette smoking-induced vascular damage still needs to be clarified. We assessed the acute effects of tobacco cigarette smoking on endothelial cell-related circulating microRNAs in healthy subjects. In addition, we investigated the potential role of microRNAs in smoking-dependent endothelial cell damage. Methods and Results A panel of endothelial-related microRNAs was quantified in healthy subjects before and after smoking 1 tobacco cigarette. Serum levels of miR-155 were found to be significantly increased shortly after smoking. We also observed a progressive and significant miR-155 accumulation in culture media of human endothelial cells after 30 minutes and up to 4 hours of cigarette smoke condensate treatment in vitro without evidence of cell death, indicating that miR-155 can be released by endothelial cells in response to smoking stress. Cigarette smoke condensate appeared to enhance oxidative stress and impair cell survival, angiogenesis, and NO metabolism in human endothelial cells. Notably, these effects were abrogated by miR-155 inhibition. We also observed that miR-155 inhibition rescued the deleterious effects of cigarette smoke condensate on endothelial-mediated vascular relaxation and oxidative stress in isolated mouse mesenteric arteries. Finally, we found that exogenous miR-155 overexpression mimics the effects of smoking stress by inducing the upregulation of inflammatory markers, impairing angiogenesis and reducing cell survival. These deleterious effects were associated with downregulation of vascular endothelial growth factor and endothelial NO synthetase. Conclusions Our results suggest that miR-155 dysregulation may contribute to the deleterious vascular effects of tobacco smoking.

Inhibition of miR-155 attenuates detrimental vascular effects of tobacco cigarette smoking / Frati, Giacomo; Forte, Maurizio; di Nonno, Flavio; Bordin, Antonella; Chimenti, Isotta; Picchio, Vittorio; Cavarretta, Elena; Stanzione, Rosita; Bianchi, Franca; Carnevale, Roberto; Nocella, Cristina; Schiavon, Sonia; Vecchio, Daniele; Marchitti, Simona; De Falco, Elena; Rubattu, Speranza; Paneni, Francesco; Biondi-Zoccai, Giuseppe; Versaci, Francesco; Volpe, Massimo; Pagano, Francesca; Sciarretta, Sebastiano. - In: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE. - ISSN 2047-9980. - 9:24(2020), pp. 1-18. [10.1161/JAHA.120.017000]

Inhibition of miR-155 attenuates detrimental vascular effects of tobacco cigarette smoking

Frati, Giacomo;Bordin, Antonella;Chimenti, Isotta;Picchio, Vittorio;Cavarretta, Elena;Stanzione, Rosita;Carnevale, Roberto;Nocella, Cristina;Schiavon, Sonia;Vecchio, Daniele;Marchitti, Simona;De Falco, Elena;Rubattu, Speranza;Paneni, Francesco;Biondi-Zoccai, Giuseppe;Volpe, Massimo;Sciarretta, Sebastiano
Ultimo
2020

Abstract

Background The role of microRNAs dysregulation in tobacco cigarette smoking-induced vascular damage still needs to be clarified. We assessed the acute effects of tobacco cigarette smoking on endothelial cell-related circulating microRNAs in healthy subjects. In addition, we investigated the potential role of microRNAs in smoking-dependent endothelial cell damage. Methods and Results A panel of endothelial-related microRNAs was quantified in healthy subjects before and after smoking 1 tobacco cigarette. Serum levels of miR-155 were found to be significantly increased shortly after smoking. We also observed a progressive and significant miR-155 accumulation in culture media of human endothelial cells after 30 minutes and up to 4 hours of cigarette smoke condensate treatment in vitro without evidence of cell death, indicating that miR-155 can be released by endothelial cells in response to smoking stress. Cigarette smoke condensate appeared to enhance oxidative stress and impair cell survival, angiogenesis, and NO metabolism in human endothelial cells. Notably, these effects were abrogated by miR-155 inhibition. We also observed that miR-155 inhibition rescued the deleterious effects of cigarette smoke condensate on endothelial-mediated vascular relaxation and oxidative stress in isolated mouse mesenteric arteries. Finally, we found that exogenous miR-155 overexpression mimics the effects of smoking stress by inducing the upregulation of inflammatory markers, impairing angiogenesis and reducing cell survival. These deleterious effects were associated with downregulation of vascular endothelial growth factor and endothelial NO synthetase. Conclusions Our results suggest that miR-155 dysregulation may contribute to the deleterious vascular effects of tobacco smoking.
2020
cardiovascular diseases; cigarette smoking; endothelial dysfunction; miR‐155; microRNAs
01 Pubblicazione su rivista::01a Articolo in rivista
Inhibition of miR-155 attenuates detrimental vascular effects of tobacco cigarette smoking / Frati, Giacomo; Forte, Maurizio; di Nonno, Flavio; Bordin, Antonella; Chimenti, Isotta; Picchio, Vittorio; Cavarretta, Elena; Stanzione, Rosita; Bianchi, Franca; Carnevale, Roberto; Nocella, Cristina; Schiavon, Sonia; Vecchio, Daniele; Marchitti, Simona; De Falco, Elena; Rubattu, Speranza; Paneni, Francesco; Biondi-Zoccai, Giuseppe; Versaci, Francesco; Volpe, Massimo; Pagano, Francesca; Sciarretta, Sebastiano. - In: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE. - ISSN 2047-9980. - 9:24(2020), pp. 1-18. [10.1161/JAHA.120.017000]
File allegati a questo prodotto
File Dimensione Formato  
Frati_Inhibition_2020.pdf

accesso aperto

Note: https://www.ahajournals.org/doi/full/10.1161/JAHA.120.017000
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.44 MB
Formato Adobe PDF
1.44 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1472641
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact