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The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction., (© 2023. The Author(s).)

Aim and Objective: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease., Materials and Methods: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology., Results: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades., Conclusion: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions., Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population., Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs., Results: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals., Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Mouse models represent a powerful tool for investigating the underlying mechanisms of disease. Type 1 diabetes results in a markedly increased risk of cardiovascular disease. The cardiovascular complications are manifested primarily as ischemic heart disease caused by accelerated atherosclerosis, but also as cardiomyopathy, defined as ventricular dysfunction in the absence of clear ischemic heart disease. Several mouse models are now available to study atherosclerosis and cardiomyopathy associated with type 1 diabetes. For studies of diabetes-accelerated atherosclerosis, these models include low-density lipoprotein (LDL) receptor-deficient and apolipoprotein E-deficient mice in which diabetes is induced by streptozotocin or viral infection. In these mouse models, type 1 diabetes can be induced without marked changes in plasma lipid levels, thereby mimicking the accelerated atherosclerosis seen in patients with type 1 diabetes. However, mouse models that exhibit thrombotic events and myocardial infarctions as a result of diabetes still need to be developed. Conversely, cardiomyopathy associated with diabetes has now been extensively evaluated in streptozotocin-treated C57BL/6 mice, and in transgenic mice expressing calmodulin under a beta-cell-specific promoter. These mouse models have given significant insight into the molecular mechanisms causing cardiomyopathy, and indicate that increased oxidative stress contributes to diabetes-associated cardiomyopathy. In this review, we will discuss the available mouse models for studies of cardiovascular complications of type 1 diabetes, the potential mechanisms underlying these complications, and the need for new and improved mouse models.

Cardiovascular diseases (CVD), including ischemic heart diseases and cerebrovascular diseases, are the leading causes of morbidity and mortality worldwide. Atherosclerosis is the major underlying factor for most CVD. It is well-established that oxidative stress and inflammation are two major mechanisms leading to atherosclerosis. Under oxidative stress, polyunsaturated fatty acids (PUFA)-containing phospholipids and cholesterol esters in cellular membrane and lipoproteins can be readily oxidized through a free radical-induced lipid peroxidation (LPO) process to form a complex mixture of oxidation products. Overwhelming evidence demonstrates that these oxidized lipids are actively involved in the inflammatory responses in atherosclerosis by interacting with immune cells (such as macrophages) and endothelial cells. In addition to lipid lowering in the prevention and treatment of atherosclerotic CVD, targeting chronic inflammation has been entering the medical realm. Clinical trials are under way to lower the lipoprotein (a) (Lp(a)) and its associated oxidized phospholipids, which will provide clinical evidence that targeting inflammation caused by oxidized lipids is a viable approach for CVD. In this review, we aim to give an update on our understanding of the free radical oxidation of LPO, analytical technique to analyze the oxidation products, especially the oxidized phospholipids and cholesterol esters in low density lipoproteins (LDL), and focusing on the experimental and clinical evidence on the role of lipid oxidation in the inflammatory responses associated with CVD, including myocardial infarction and calcific aortic valve stenosis. The challenges and future directions in understanding the role of LPO in CVD will also be discussed. Image 1 • Free radical lipid oxidation has been implicated in the pathogenesis of CVD. • Oxidized lipids modulate inflammatory responses in atherosclerosis and CVD. • Analysis of oxidized lipids by MS may identify potential biomarkers for CVD. • Targeting inflammation/oxidized lipids can be a viable approach for CVD treatment. [ABSTRACT FROM AUTHOR]