Summary
Introduction:
This text summarizes a scientific study that investigates the potential health risks of electronic cigarettes (e-cigs) on patients with pulmonary arterial hypertension (Pah). The study uses patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from healthy individuals and patients with Pah to evaluate the impact of e-cigs on endothelial dysfunction and the molecular mechanisms contributing to it.
Key Points:
* Pah iPSC-ECs show a greater amount of damage than healthy iPSC-ECs upon e-cig exposure.
* Transcriptomic analyses revealed that differential expression of akt3 may be responsible for increased autophagic flux impairment in Pah iPSC-ECs, which underlies increased susceptibility upon e-cig exposure.
* Knockdown of akt3 in healthy iPSC-ECs significantly induces autophagic flux impairment and endothelial dysfunction, which further increases with e-cig treatment.
* Functional disruption of mTORC2 by knocking down Rictor in Pah iPSC-ECs causes autophagic flux impairment, which is mediated by downregulation of akt3.
* Pharmacological induction of autophagy via direct inhibition of mTORC1 and indirect activation of mTORC2 with rapamycin reverses e-cig-induced decreased akt3 expression, endothelial dysfunction, autophagic flux impairment, and decreased cell viability and migration in Pah iPSC-ECs.
Main Message:
The study suggests a potential link between autophagy and akt3-mediated increased susceptibility to e-cigs in Pah. The findings highlight the importance of considering the potential risks of e-cigs on patients with preexisting health concerns, such as Pah, and the need for further research to better understand the underlying molecular mechanisms. The study also demonstrates the potential of using patient-specific iPSC-ECs to model diseases and evaluate the impact of e-cigs on endothelial dysfunction.
Citation
Liu CW, Le hhT, Denaro P, et al. E-cigarettes Induce Dysregulation of autophagy Leading to Endothelial Dysfunction in Pulmonary arterial hypertension. Stem cells (Dayton, Ohio). 2023;41(4):328-340. doi:10.1093/stmcls/sxad004
