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We explored physiological effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on intact experimentally hypertrophic murine hearts following transverse aortic constriction (TAC). Postoperative drug (2–6 weeks) challenge resulted in reduced late Na+ currents, and increased phosphorylated (p-)CaMK-II and Nav1.5 but not total (t)-CaMK-II, and Na+/Ca2+ exchanger expression, confirming previous cardiomyocyte-level reports. It rescued TAC-induced reductions in echocardiographic ejection fraction and fractional shortening, and diastolic anterior and posterior wall thickening. Dual voltage- and Ca2+-optical mapping of Langendorff-perfused hearts demonstrated that empagliflozin rescued TAC-induced increases in action potential durations at 80% recovery (APD80), Ca2+ transient peak signals and durations at 80% recovery (CaTD80), times to peak Ca2+ (TTP100) and Ca2+ decay constants (Decay30–90) during regular 10-Hz stimulation, and Ca2+ transient alternans with shortening cycle length. Isoproterenol shortened APD80 in sham-operated and TAC-only hearts, shortening CaTD80 and Decay30–90 but sparing TTP100 and Ca2+ transient alternans in all groups. All groups showed similar APD80, and TAC-only hearts showed greater CaTD80, heterogeneities following isoproterenol challenge. Empagliflozin abolished or reduced ventricular tachycardia and premature ventricular contractions and associated re-entrant conduction patterns, in isoproterenol-challenged TAC-operated hearts following successive burst pacing episodes. Empagliflozin thus rescues TAC-induced ventricular hypertrophy and systolic functional, Ca2+ homeostatic, and pro-arrhythmogenic changes in intact hearts. [ABSTRACT FROM AUTHOR]

Background While there is some evidence and conceptual plausibility that tobacco product use is associated with hypertension incidence and that this association varies by sex, extant longitudinal research had been conducted prior to the emergence of e-cigarette and dual e-cigarette and cigarette use. Aims and Methods Data were analyzed from the US Population Assessment of Tobacco and Health study for adults with no lifetime history of hypertension at wave 1 (2013–2014) who completed waves 2–4 follow-up surveys (2014–2018; n = 16 434). Sex-stratified weighted covariate-adjusted multivariable Cox regression models were used to examine the association between established current e-cigarette or cigarette exclusive or dual-use (as a time-varying and time-lagged regressor) and subsequent self-reported hypertension onset. Results Weighted cumulative hypertension incidence by wave 4 varied by waves 1–3 e-cigarette, cigarette, and dual use status in females (nonuse [incidence: 9.9%], exclusive e-cigarette use [11.8%], exclusive cigarette use [14.8%], dual-use [12.4%]; p =.003 for omnibus differences among all groups) but not males (nonuse [12.6%], exclusive e-cigarette use [9.7%], exclusive cigarette use [13.7%], dual-use [9.3%]; p =.231). Among females, exclusive cigarette (vs. no) use (hazard ratio: 1.69, 95%CI 1.21 to 2.34; p =.002), but not exclusive e-cigarette or dual-use, was significantly associated with subsequent hypertension. Dose–response models were suggestive that consistent exclusive e-cigarette or dual-use versus nonuse across multiple may be associated with hypertension among females, but results were nonsignificant. Conclusions The association of e-cigarette, cigarette, and dual use with hypertension may differ by sex, whereby exclusive cigarette use could be a prospective risk factor for subsequent self-reported hypertension in US adult females. Implications This nationally representative cohort study provides the very first evidence of whether there are prospective associations of established e-cigarette and cigarette use and dual use with future hypertension onset among US adult females and males. We found that exclusive cigarette smoking was associated with an increased risk of incident hypertension among females, but not males. We observed a trend of a dose–response relationship between e-cigarette use and risk of incident hypertension among female exclusive e-cigarette users or dual e-cigarette and cigarette users. Our study will contribute to understanding the chronic health risks of vaping to prevent the potential long-term e-cigarette use-related health burden. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prevailing data suggest that ATP-sensitive potassium channels (KATP) contribute to a surprising resistance to hypoxia in mammalian embryos, thus we aimed to characterize the developmental changes of KATP channels in murine fetal ventricular cardiomyocytes. Methods: Patch clamp was applied to investigate the functions of KATP. RT-PCR, Western blot were used to further characterize the molecular properties of KATP channels. Results: Similar KATP current density was detected in ventricular cardiomyocytes of late development stage (LDS) and early development stage (EDS). Molecular–biological study revealed the upregulation of Kir6.1/SUR2A in membrane and Kir6.2 remained constant during development. Kir6.1, Kir6.2, and SUR1 were detectable in the mitochondria without marked difference between EDS and LDS. Acute hypoxia–ischemia led to cessation of APs in 62.5% of tested EDS cells and no APs cessation was observed in LDS cells. SarcKATP blocker glibenclamide rescued 47% of EDS cells but converted 42.8% of LDS cells to APs cessations under hypoxia-ischemic condition. MitoKATP blocker 5-HD did not significantly influence the response to acute hypoxia–ischemia at either EDS or LDS. In summary, sarcKATP played distinct functional roles under acute hypoxia-ischemic condition in EDS and LDS fetal ventricular cardiomyocytes, with developmental changes in sarcKATP subunits. MitoKATP were not significantly involved in the response of fetal cardiomyocytes to acute hypoxia–ischemia and no developmental changes of KATP subunits were found in mitochondria. [Copyright &y& Elsevier]

Heart failure (HF) is a prevalent cardiovascular disease with significant morbidity and mortality rates worldwide. Due to the intricate structure of the heart, diverse cell types, and the complex pathogenesis of HF, further in-depth investigation into the underlying mechanisms  is required. The elucidation of the heterogeneity of cardiomyocytes and the intercellular communication network is particularly important. Traditional high-throughput sequencing methods provide an average measure of gene expression, failing to capture the "heterogeneity" between cells and impacting the accuracy of gene function knowledge. In contrast, single-cell sequencing techniques allow for the amplification of the entire genome or transcriptome at the individual cell level, facilitating the examination of gene structure and expression with unparalleled precision. This approach offers valuable insights into disease mechanisms, enabling the identification of changes in cellular components and gene expressions during hypertrophy associated with HF. Moreover, it reveals distinct cell populations and their unique roles in the HF microenvironment, providing a comprehensive understanding of the cellular landscape that underpins HF pathogenesis. This review focuses on the insights provided by single-cell sequencing techniques into the mechanisms underlying HF and discusses the challenges encountered in current cardiovascular research., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)