Biology subjects

Chidipi, B.

Publications and source records attributed to Chidipi, B..

3 recordsLinked to original sources

bioRxiv2025

Oxidative stress mediates cardiac electrophysiological injury in inhalation exposure to flavored vaping products.

BackgroundElectronic nicotine delivery systems (ENDS) heat "E-liquids" to generate "E-vapor", an aerosolized mixture containing nicotine and flavors. Flavored ENDS are popular among teens who vape, however, the possible cardiac electrophysiological harm of inhalation exposure to flavored ENDS are not fully understood. ObjectiveTo test if inhalation exposure to flavoring carbonyls in E-liquids compromises mitochondrial integrity, increases oxidative stress, and leads to cardiac electrophysiological toxicity. MethodsGas chromatography mass spectrometry (GC/MS), flow cytometry, oxygen consumption rate (OCR) measurement, in-vivo programmed electrical stimulation (PES), and multielectrode array (MEA) were used in atrial like HL-1 myocytes, hiPSC derived cardiomyocytes, and mice overexpressing mitochondrial catalase (mCAT). ResultsWe compared the toxicity of E-vapor exposure from 30 differently flavored E-liquids in HL-1 cells using apoptotic annexin V flow cytometry. Most E-liquids were toxic. We identified the major flavoring carbonyls in these E-liquids and quantified their concentrations using GC/MS. Linear regression analysis showed that toxicity correlated with carbonyls concentration. Using flow cytometry of CellROX and TMRE staining, HL-1 cells exposed to flavored E-vapor showed increased reactive oxygen species and depolarized mitochondrial membrane potential. Additionally, exposure decreased OCR in these cells. In-vivo inhalation exposure to flavored E-vapor increased the inducible ventricular tachycardia duration in WT but not in mCAT mice compared to controls. MEA recordings in hiPSC derived cardiomyocytes exposed to flavored E-vapor, with or without nicotine, resulted in changes in the spontaneous beating rate. ConclusionsInhalation exposure to flavored ENDS negatively affects ventricular electrophysiology, in part via adverse mitochondrial remodeling, and increased oxidative stress.

physiology↗

bioRxiv2023

The Cardiac Calcium Handling Machinery is Remodeled in Friedreich's Ataxia

BackgroundFriedreichs ataxia (FA) is an inherited neurodegenerative disorder that causes progressive nervous system damage resulting in impaired muscle coordination. FA is the most common autosomal recessive form of ataxia and is caused by an expansion of the DNA triplet guanine-adenine-adenine (GAA) in the first intron of the Frataxin gene (FXN), located on chromosome 9q13. In the unaffected population, the number of GAA repeats ranges from 6 to 27 repetitions. In FA patients, GAA repeat expansions range from 44 to 1,700 repeats which decreases frataxin protein expression. Frataxin is a mitochondrial protein essential for various cellular functions, including iron metabolism. Reduced frataxin expression is thought to negatively affect mitochondrial iron metabolism, leading to increased oxidative damage. Although FA is considered a neurodegenerative disorder, FA patients display heart disease that includes hypertrophy, heart failure, arrhythmias, conduction abnormalities, and cardiac fibrosis. ObjectiveIn this work, we investigated whether abnormal Ca2+ handling machinery is the molecular mechanism that perpetuates cardiac dysfunction in FA. MethodsWe used the frataxin knock-out (FXN-KO) mouse model of FA as well as human heart samples from donors with FA and from unaffected donors. ECG and echocardiography were used to assess cardiac function in the mice. Expression of calcium handling machinery proteins was assessed with proteomics and western blot. In left ventricular myocytes from FXN-KO and FXN-WT mice, the IonOptix system was used for calcium imaging, the seahorse assay was utilized to measure oxygen consumption rate (OCR), and confocal imaging was used to quantify the mitochondrial membrane potential ({Delta}{psi}m) and reactive oxygen species (ROS). ResultsWe found that major contractile proteins, including SERCA2a and Ryr2, were downregulated in human left ventricular samples from deceased donors with FA compared to unaffected donors, similar to the downregulation of these proteins in the left ventricular tissue from FXN-KO compared to FXN-WT. On the ECG, the RR, PR, QRS, and QTc were significantly longer in the FXN-KO mice compared to FXN-WT. The ejection fraction and fractional shortening were significantly decreased and left ventricular wall thickness and diameter were significantly increased in the FXN-KO mice versus FXN-WT. The mitochondrial membrane potential {Delta}{psi}m was depolarized, ROS levels were elevated, and OCR was decreased in ventricular myocytes from FXN-KO versus FXN-WT. ConclusionThe development of left ventricular contractile dysfunction in FA is associated with reduced expression of calcium handling proteins and mitochondrial dysfunction.

physiology↗

bioRxiv2019

Vaping Perpetuates Cardiac Electrical Instability

BackgroundTobacco cigarette smoking is on the decline, but the usage of electronic nicotine delivery systems (ENDS) is gaining popularity, specifically in the teen and young adult age groups. While the cardiac toxicity of tobacco cigarette smoking has been widely studied and is well established, the possible cardiac toxicity of ENDS products and their design characteristics, such as added flavorings, are largely underexplored. Vaping, a form of electronic nicotine delivery, uses "e-liquid" to generate "e-vapor", a smoke-like aerosolized mixture of nicotine and flavors. Here, we tested the hypothesis that vaping results in cardiac electrophysiological instability and arrhythmogenesis. We thus investigated how e-liquids with different flavors affect cardiac in-vitro and in-vivo toxicity, in cell culture and in animals. MethodsThree e-liquids with vanilla, cinnamon or fruit flavors were studied. We quantified apoptosis and oxygen consumption rate in HL-1 cells cultured with e-vapors extracts. In human iPSC derived ventricular cardiomyocytes (hiPSC-CM) cultured with e-vapor extract, beating frequency and repolarization duration were measured using multiple electrode arrays (MEA). Mass spectrometry (GC-MS) was used to analyze the composition of the e-vapors. Telemetric ECGs were obtained in freely moving C57BL/6J mice exposed to vanilla flavored e-vapor for 10 weeks and heart rate variability was analyzed (HRV). In-vivo inducibility of ventricular tachycardia as well as optical mapping of voltage in isolated Langendorff-perfused hearts were also carried out. ResultsE-vapor caused a dose dependent increase in toxicity in Hl-1 myocytes and e-vapors containing vanilla and cinnamon flavorings, as indicated by GC-MS, were more toxic, and inhibited cellular respiration more than the fruit flavored e-vapor. In hiPSC-CM cultured with 25% cinnamon flavored e-vapor for 24 hours, beating frequency increased, and the field potential duration significantly increased compared to air control. Inhalation exposure to vanilla flavored e-vapor for 10 weeks caused significant effects on HRV. Additionally, inducible VT was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the exposed mice compared to control ConclusionThe widely popular flavored ENDS are not harm free, and they show potential toxicity to the heart, in-vitro, and in vivo. Further studies are needed to further assess their cardiac safety profile, and long-term health effects.

physiology↗