Background: The epicardial adipose tissue (EAT) of metabolic syndrome (MetS) is abnormally accumulated with dysfunctional secretion of adipokines, closely relating to cardiac dysfunction. The current study was designed to identify the effects of EAT‐derived leptin on the myocardium of MetS rats and explore the potential molecular mechanisms. Methods and Results: A MetS rat model was established in 8‐week‐old Wistar rats by a 12‐week high‐fat diet. MetS rats exhibited increased leptin secretion from EAT, cardiac hypertrophy, and diastolic dysfunction with preserved systolic function. The myocardium of MetS rats had abnormal structure, increased oxidative stress injury, and higher inflammatory factor levels, especially the subepicardial myocardium, which was correlated with the EAT‐derived leptin level but not the serum leptin. The EAT was separated from each group of rats to prepare EAT‐conditioned medium. H9C2 rat cardiomyoblasts were treated with EAT‐conditioned medium or leptin, plus various inhibitors. EAT‐derived leptin from MetS rats promoted mitochondrial oxidative stress and dysfunction, induced mitochondrial pathway apoptosis, and inhibited cell viability in H9C2 cardiomyoblasts via the protein kinase C/reduced nicotinamide adenine dinucleotide phosphate oxidase/reactive oxygen species (PKC/NADPH oxidase/ROS) pathway. EAT‐derived leptin from MetS rats stimulated inflammation in H9C2 cardiomyocytes by promoting activator protein 1 nuclear translocation via the PKC/NADPH oxidase/ROS pathway. Leptin promoted the interaction between p‐p47 ^phox and gp91 ^phox in H9C2 cardiomyocytes via protein kinase C, activating nicotinamide adenine dinucleotide phosphate oxidase, increasing reactive oxygen species generation, and inhibiting cell viability. Conclusions: EAT‐derived leptin induces MetS‐related myocardial injury through the following 2 cooperative ways via PKC/NADPH oxidase/ROS pathway: (1) inducing mitochondrial pathway apoptosis by promoting mitochondrial oxidative stress and dysfunction; and (2) stimulating inflammation by promoting activator protein 1 nuclear translocation.

Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia ( , 95% confidence interval (CI) (1.31-1.79), ) and pre-eclampsia ( , 95% CI (1.28-1.77), ); T cell absolute count was causally associated with total eclampsia ( , 95% CI (1.28-1.73), ) and pre-eclampsia ( , 95% CI (1.25-1.72), ). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia ( , 95% CI (1.44-2.32), ) and pre-eclampsia (