Empagliflozin restores cardiac metabolism and suppresses immune activation in acute myocardial infarction.

Background And Aims: Empagliflozin (EMPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), is cardioprotective in acute myocardial infarction (AMI) including fewer hospitalizations for heart failure. However, the underlying metabolic and immunomodulatory mechanisms remain incompletely characterized. This study investigates the metabolic effects of EMPA in diabetic and non-diabetic conditions, as well as on AMI-induced immune responses.

Hepato-cardiac interorgan communication controls cardiac hypertrophy via combined endocrine-autocrine FGF21 signaling.

Fibroblast growth factor (FGF) 21 is a hormone produced mainly by the liver but also other organs, including the heart. Although FGF21 analogs are used for treating obesity and metabolic syndrome in humans, preclinical and clinical studies have elicited mixed results about whether prolonged FGF21 signaling is protective or detrimental for cardiac function. Based on our findings, showing elevated serum and cardiac FGF21 levels in humans with increased left ventricular afterload, we explore the involvement of FGF21 in cardiac hypertrophy.

Cardiac ischaemia/reperfusion in pigs and mice increases cardiomyocyte Krüppel-like factor 5 that aggravates tissue injury and remodelling.

Aims: Activation of the transcriptional factor Krüppel-like factor 5 (KLF5) is detrimental to chronic heart failure. We explored the involvement of KLF5 in myocardial ischaemia/reperfusion injury.

Methods And Results: Yorkshire pigs underwent 75' of ischaemia, followed by 3 or 24 h of reperfusion.

Sex-Related Effects on Cardiac Development and Disease.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality. Interestingly, male and female patients with CVD exhibit distinct epidemiological and pathophysiological characteristics, implying a potentially important role for primary and secondary sex determination factors in heart development, aging, disease and therapeutic responses. Here, we provide a concise review of the field and discuss current gaps in knowledge as a step towards elucidating the "sex determination-heart axis".

Developmental and regenerative biology of cardiomyocytes.

Current progress and challenges in understanding the molecular and cellular mechanisms of cardiomyocyte embryonic development and regeneration are reviewed in our present work. Three major topics are critically discussed: how do cardiomyocytes form in the embryo? What is the adult origin of the cells that regenerate cardiomyocytes in animal models with adult heart regeneration capabilities? Can the promise of therapeutic cardiomyocyte regeneration be realized in humans? In the first topic, we highlight current advances in understanding the developmental biology of cardiomyocytes, with emphasis on the regulative capabilities of the early embryo during specification and allocation of the cardiomyoblasts that produce the primordial heart. We place further emphasis on trabecular cardiomyocyte development from late cardiomyoblasts, neural crest cells and primordial cardiomyocytes, and their critical role in the clonal growth of the compact/septal and cortical cardiomyocyte layers in the mammalian embryo and adult zebrafish, respectively.