Franklinguy9946

Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. We aimed to identify candidate angiocrines expressed by endocardial and ECs inwildtype and LVNC conditions in Tie2Cre;Ino80fl/fl transgenic embryonic mouse hearts, and test the effect of these candidates on cardiomyocyte proliferation and maturation.

We used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. learn more We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15A1 as a coronary vessel-secreted angiocrine factor, downregulated by Ino80-deficiency, that functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells (ECs) up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation.

These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.

These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.

The aim of this study is to summarize data from prospective cohort studies on clinical predictors of stroke and systemic embolism in anticoagulant-naïve atrial fibrillation (AF) patients.

EMBASE, MEDLINE, Global Index Medicus, and Web of Science were searched to identify all studies published by 28 November 2019. Forty-seven studies reporting data from 1 756 984 participants in 15 countries were included. The pooled incidence of stroke in anticoagulant-naïve AF patients was 23.8 per 1000 person-years (95% CI 19.7-28.2). Older age was associated with incident stroke or systemic embolism, with a pooled hazard ratio (HR) of 2.14 (95% CI 1.85-2.47), 2.83 (95% CI 2.27-3.51), and 6.87 (95% CI 6.33-7.44) for age 65-75, ≥75, and ≥85 years, respectively. Other predictors of stroke or systemic embolism included history of stroke or TIA (HR 2.84, 95% CI 2.19-3.67), hypertension (HR 1.60, 95% CI 1.37-1.86), diabetes (HR 1.28, 95% CI 1.20-1.37), heart failure (HR 1.25, 95% CI 1.11-1.40), peripheral artery disease (pooled HR 1.35, 95% CI 1.04-1.75), vascular disease (pooled HR 1.21, 95% CI 1.06-1.39), and prior myocardial infarction (pooled HR 1.08, 95% CI 1.03-1.14). Female sex was a predictor of thromboembolism in studies outside Asia (HR 1.33, 95% CI 1.15-1.55), but not in those done in Asia (HR 0.95, 95% CI 0.81-1.10).

This study confirms age and prior stroke as the strongest predictors of stroke or systemic embolism in anticoagulant-naive AF patients. Other predictors include hypertension, diabetes, heart failure, and vascular disease. Female sex seems not to be universally associated with stroke or systemic embolism.

This study confirms age and prior stroke as the strongest predictors of stroke or systemic embolism in anticoagulant-naive AF patients. Other predictors include hypertension, diabetes, heart failure, and vascular disease. Female sex seems not to be universally associated with stroke or systemic embolism.Sulfur is an essential component of various biologically important molecules, including methionine, cysteine and glutathione, and it is also involved in coping with oxidative and heavy metal stress. Studies using model organisms, including budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe), have contributed not only to understanding various cellular processes but also to understanding the utilization and response mechanisms of each nutrient, including sulfur. Although fission yeast can use sulfate as a sulfur source, its sulfur metabolism pathway is slightly different from that of budding yeast because it does not have a trans-sulfuration pathway. In recent years, it has been found that sulfur starvation causes various cellular responses in S. pombe, including sporulation, cell cycle arrest at G2, chronological lifespan extension, autophagy induction and reduced translation. This MiniReview identifies two sulfate transporters in S. pombe, Sul1 (encoded by SPBC3H7.02) and Sul2 (encoded by SPAC869.05c), and summarizes the metabolic pathways of sulfur assimilation and cellular response to sulfur starvation. Understanding these responses, including metabolism and adaptation, will contribute to a better understanding of the various stress and nutrient starvation responses and chronological lifespan regulation caused by sulfur starvation.The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to be incorporated into clinical practice. In the absence of specific indications for chronic oral anticoagulation due to concomitant cardiovascular disease, a single antiplatelet agent is the basis for long-term antithrombotic treatment in patients with aortic or peripheral arterial diseases. Its association with another antiplatelet agent or low-dose anticoagulants will be discussed, based on patient's ischaemic and bleeding risk as well therapeutic paths (e.g. endovascular therapy). This consensus document aims to provide a guidance for antithrombotic therapy according to arterial disease localizations and clinical presentation.