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Exposure to serum from exclusive heated tobacco product smokers induces mTOR activation and fibrotic features in human cardiac stromal cells.
Picchio, Vittorio; Pagano, Francesca; Carnevale, Roberto; D'Amico, Alessandra; Cozzolino, Claudia; Floris, Erica; Bordin, Antonella; Schirone, Leonardo; Vecchio, Daniele; Saade, Wael; Miraldi, Fabio; De Falco, Elena; Sciarretta, Sebastiano; Peruzzi, Mariangela; Biondi-Zoccai, Giuseppe; Frati, Giacomo; Chimenti, Isotta.
Affiliation
  • Picchio V; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
  • Pagano F; Institute of Biochemistry and Cell Biology, National Council of Research (IBBC-CNR), Monterotondo, Italy.
  • Carnevale R; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
  • D'Amico A; Department of Movement, Human, and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
  • Cozzolino C; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.
  • Floris E; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.
  • Bordin A; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.
  • Schirone L; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
  • Vecchio D; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy.
  • Saade W; Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University, Rome, Italy.
  • Miraldi F; Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University, Rome, Italy.
  • De Falco E; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.
  • Sciarretta S; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
  • Peruzzi M; Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University, Rome, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.
  • Biondi-Zoccai G; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.
  • Frati G; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
  • Chimenti I; Department of Medical Surgical Sciences and Biotechnologies, Sapienza University, Latina, Italy; Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy. Electronic address: isotta.chimenti@uniroma1.it.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167350, 2024 10.
Article in En | MEDLINE | ID: mdl-39002704
ABSTRACT
Chronic smokers have increased risk of fibrosis-related atrial fibrillation. The use of heated-tobacco products (HTPs) is increasing exponentially, and their health impact is still uncertain. We aim to investigate the effects of circulating molecules in exclusive HTP chronic smokers on the fibrotic behavior of human atrial cardiac stromal cells (CSCs). CSCs were isolated from atrial tissue of elective cardiac surgery patients, and exposed to serum lots from young healthy subjects, stratified in exclusive HTP smokers, tobacco combustion cigarette (TCC) smokers, or nonsmokers (NS). CSCs treated with TCC serum displayed impaired migration and increased expression of pro-inflammatory cytokines. Cells cultured with HTP serum showed increased levels of pro-fibrotic markers, and reduced expression of connexin-43. Both TCC and HTP sera increased collagen release and reduced secretion of angiogenic protective factors from CSCs, compared to NS serum. Paracrine support to tube-formation by endothelial cells and to viability of cardiomyocytes was significantly impaired. Treatment with sera of both smokers groups impaired H2O2/NO release balance by CSCs and reduced early phosphorylation of several pathways compared to NS serum, leading to mTOR activation. Cotreatment with rapamycin was able to reduce mTOR phosphorylation and differentiation into aSMA-positive myofibroblasts in CSCs exposed to TCC and HTP sera. In conclusion, the circulating molecules in the serum of chronic exclusive HTP smokers induce fibrotic behavior in CSCs through activation of the mTOR pathway, and reduce their beneficial paracrine effects on endothelial cells and cardiomyocytes. These results point to a potential risk for cardiac fibrosis in chronic HTP users.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fibrosis / TOR Serine-Threonine Kinases / Tobacco Products Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Biochim Biophys Acta Mol Basis Dis Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Fibrosis / TOR Serine-Threonine Kinases / Tobacco Products Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Biochim Biophys Acta Mol Basis Dis Year: 2024 Document type: Article Affiliation country: Country of publication: