Abstract
Background Cigarette smoke can trigger calcium influx in cardiac myocytes that over time can lead to cardiovascular diseases linked to calcium handling such as atrial fibrillation and heart failure. E-cigarette vapor, similar to cigarette smoke, contains aldehydes that trigger intracellular calcium in neurons. Further, ~560 million people carry an inactivating genetic variant in aldehyde dehydrogenase 2 (ALDH2), known as ALDH2*2, the primary enzyme responsible for metabolizing acetaldehyde. However, little is known how acetaldehyde present in cigarette smoke and e-cigarette aerosol, when coupled with genetics, influence intracellular calcium release within the cardiac myocyte. Hypothesis: Acetaldehyde in e-cigarette aerosol and cigarette smoke can trigger calcium influx in cardiac myocytes. Methods: ALDH2 expression and activity were quantified from wild type ALDH2 and ALDH2*2 male mice heart homogenates. Further, ALDH2 and ALDH2*2 primary adult cardiac myocytes were treated with a short burst of acetaldehyde (0.1-100 μM for 30 seconds, to recapitulate vaping or smoking) and intracellular calcium levels were assessed by fura-2 (5 μM). A Student's t-test was used to compare responses between rodents with significance *p<0.05. Results: The enzymatic activity to metabolize aldehydes within the heart was 3-fold lower for the ALDH2*2 relative to ALDH2 heart homogenates (0.14±0.003* versus 0.45±0.02, ALDH2/GAPDH relative densitometry units, n=3/group). Further, acetaldehyde (0.1 μM) triggered intracellular calcium influx that was 5-fold higher for ALDH2*2 myocytes compared to ALDH2 myocytes (8.32±0.72 %* versus 1.46±0.31%, percent of maximal response, n=4-6 cells from 4 biological replicates). Peak intracellular calcium influx was also ~40% higher for ALDH2*2 myocytes when compared to wild type ALDH2 myocytes over a range of additional acetaldehyde doses (0.1-100 μM) tested. Conclusion: Acetaldehyde, the primary aldehyde in e-cigarette aerosol, triggers intracellular calcium influx that is ~40% greater for rodents carrying an inactivating ALDH2 variant, ALDH2*2. People carrying an inactive ALDH2*2 genetic variant may be more susceptible to acetaldehyde present within e-cigarette vapor and cigarette smoke which over time and continued use lead to developing cardiovascular diseases linked to altered calcium handling.
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