Atrial fibrillation (AF) is strongly associated with strokes, heart failure, and increased mortality. This study aims to identify the monocyte-macrophage heterogeneity and interactions of these cells with non-immune cells, and to identify functional biomarkers in patients with AF. Therefore, we assess the single cell landscape of left atria (LA), using a combination of single cell and nucleus RNA-seq.
View Article and Find Full Text PDFThe 88Annual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8to Sunday, March 10in Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion.
View Article and Find Full Text PDFThere is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq).
View Article and Find Full Text PDFBackground: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS.
View Article and Find Full Text PDFAlzheimer's disease (AD) is among the most prevalent age-related neurodegenerative diseases. Endothelial cell (EC) senescence was discovered in the AD brain, but its function in AD pathogenesis was unidentified. Here we created an AD mouse model with EC senescence (APP/PS1;TERF2DN mice) by intercrossing APP/PS1 mice with Tie2 promoter-driven dominant negative telomeric repeat-binding factor 2 transgenic mice (TERF2DN-Tg mice).
View Article and Find Full Text PDFBody mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination dataset over time (2012-2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH).
View Article and Find Full Text PDFBackground: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease characterized by dilated abdominal aorta. Immune cells have been shown to contribute to the development of AAA, and that the gut microbiota is associated with numerous diseases, including cardiovascular diseases, by regulating immune systems or metabolic pathways of the host. However, the interaction between the gut microbiota and AAA remains unknown.
View Article and Find Full Text PDFBackground: The impact of body mass index (BMI) on hospital mortality in patients with acute heart failure has been well documented in Asian populations. However, the relationship between BMI, hospital-associated disability (HAD), and hospitalization costs in patients with heart failure is poorly understood. This study aimed to explore the impact of BMI on HAD and hospitalization costs for acute heart failure in Japan.
View Article and Find Full Text PDFBackground: Drug-coated balloon angioplasty after directional coronary atherectomy (DCA) allows for a stentless strategy providing good short-term outcomes; however, late-phase restenosis and its mechanism remain unclear. Moreover, histopathological evaluation for late-phase restenosis post-drug-coated balloon angioplasty after DCA has never been reported.
Case Summary: We report the first case of late-phase restenosis post-drug-coated balloon angioplasty after DCA, wherein tissue analysis using intravascular coronary imaging and histopathology suggested neovascularization in newly developed neointimal proliferation.
Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood.
View Article and Find Full Text PDFThe gut microbiome has emerged as a key regulator of obesity; however, its role in brown adipose tissue (BAT) metabolism and association with obesity remain to be elucidated. We found that the levels of circulating branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) were significantly correlated with the body weight in humans and mice and that BCAA catabolic defects in BAT were associated with obesity in diet-induced obesity (DIO) mice. Pharmacological systemic enhancement of BCAA catabolic activity reduced plasma BCAA and BCKA levels and protected against obesity; these effects were reduced in BATectomized mice.
View Article and Find Full Text PDFBackground: We had previously reported an increase in trimethylamine N-oxide (TMAO) levels in patients with both compensated and decompensated heart failure (HF) and alteration in gut microbiota composition using 16S rRNA gene amplicon analysis. Although a metagenome-wide analysis showed that choline-TMA lyase levels increased in HF patients, which TMA generation pathway from choline, carnitine, or betaine contributes to the increase in TMAO levels in HF needs to be elucidated.
Methods: We conducted a metagenome-wide shotgun sequencing analysis of gut microbiota and measured the TMAO levels in plasma of 22 HF patients during the compensated phase and 11 age-, sex-, and comorbidity-matched control subjects, whose gut microbiota compositions were reported in a previous 16S rRNA-based analysis.
Cardiovascular diseases (CVDs) have become a major health problem because of the associated high morbidity and mortality rates observed in affected patients. Gut microbiota has recently been implicated as a novel endocrine organ that plays critical roles in the regulation of cardiometabolic and renal functions of the host via the production of bioactive metabolites. This review investigated the evidence from several clinical and experimental studies that indicated an association between the gut microbiota-derived toxins and CVDs.
View Article and Find Full Text PDFRationale: Bone marrow transplantation (BMT) is used frequently to study the role of hematopoietic cells in atherosclerosis, but aortic arch lesions are smaller in mice after BMT.
Objective: To identify the earliest stage of atherosclerosis inhibited by BMT and elucidate potential mechanisms.
Methods And Results: mice underwent total body γ-irradiation, bone marrow reconstitution, and 6-week recovery.
Faecal lipopolysaccharides (LPS) have attracted attention as potent elements to explain a correlation between the gut microbiota and cardiovascular disease (CVD) progression. However, the underlying mechanism of how specific gut bacteria contribute to faecal LPS levels remains unclear. We retrospectively analysed the data of 92 patients and found that the abundance of the genus Bacteroides was significantly and negatively correlated with faecal LPS levels.
View Article and Find Full Text PDFLaparoscopic sleeve gastrectomy (LSG) is an important therapeutic option for morbidly obese patients. Although LSG promotes sufficient weight loss, how LSG changes plasma metabolites remains unclear. We assessed changes in plasma metabolite levels after LSG.
View Article and Find Full Text PDFVascular inflammation via T-cell-mediated immune responses has been shown to be critically involved in the pathogenesis of abdominal aortic aneurysm (AAA). T-cell coinhibitory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is known to act as a potent negative regulator of immune responses. However, the role of this molecule in the development of AAA remains completely unknown.
View Article and Find Full Text PDFMechanisms that govern transcriptional regulation of inflammation in atherosclerosis remain largely unknown. Here, we identify the nuclear transcription factor c-Myb as an important mediator of atherosclerotic disease in mice. Atherosclerosis-prone animals fed a diet high in cholesterol exhibit increased levels of c-Myb in the bone marrow.
View Article and Find Full Text PDFBackground: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis.
View Article and Find Full Text PDFBackground: Gut microbiome composition or circulating microbiome-related metabolites in patients with heart failure (HF) have not been investigated at different time points (i.e., in the decompensated (Decomp) and compensated (Comp) phases).
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