Electronic cigarette extract induced toxic effect in iPS-derived cardiomyocytes

Area of Science:

• Cardiology
• Toxicology
• Cell Biology

Background:

• Cigarette smoking is a known risk factor for cardiovascular diseases.
• Electronic cigarettes (ECs) are often perceived as safer alternatives, but their impact on cardiac health requires thorough investigation.
• This study compares the cardiotoxicity of electronic cigarette extract (ECE) and conventional cigarette smoke extract (CSE).

Purpose of the Study:

• To assess and compare the cellular toxic effects of ECE and CSE on cardiomyocytes.
• To investigate the impact of acute and chronic exposure to ECE and CSE on cardiomyocyte function and viability.
• To analyze the molecular changes, including gene expression, induced by ECE and CSE exposure in cardiomyocytes.

Main Methods:

• Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to ECE and CSE.
• Nicotine concentrations and other ingredients in ECE and CSE were quantified using Mass-Spectrometry and Q-Exactive-HF.
• Cellular reactive oxygen species (ROS) production, myocyte motility, beat frequency, and cell viability were measured.
• Gene expression profiles of heart failure-related genes were analyzed post-exposure.

Main Results:

• ECE exhibited similar cardiotoxicity to CSE, despite significantly lower nicotine content in ECE.
• Both ECE and CSE induced significant oxidative stress (ROS production) in cardiomyocytes.
• Exposure to both ECE and CSE led to decreased cardiomyocyte beating frequency, increased cell death, and reduced long-term viability.
• Gene expression analysis revealed distinct patterns in ECE- and CSE-exposed cells, implicating pathways in cell proliferation, inflammation, and apoptosis.

Conclusions:

• Electronic cigarette extract (ECE) and conventional cigarette smoke extract (CSE) induce comparable cardiotoxic effects.
• These toxicities include oxidative stress, impaired cardiomyocyte function (negative chronotropic effects), altered myocardial gene expression, and cell death.
• The findings highlight potential cardiac risks associated with both conventional and electronic cigarette use, irrespective of nicotine concentration differences.