Antibodies to oxidation-specific epitopes characterize hemodialysis patients protected from cardiovascular events.

Background: Despite the high risk of cardiovascular disease (CVD) in patients on hemodialysis (HD), some appear protected from CVD-associated mortality and survive long-term on HD. The immune system can recognize oxidation-specific epitopes (OSEs) and create antibodies with pro- or antithrombotic properties. This study aimed to elucidate the role of natural antibodies against OSEs in patients on hemodialysis (HD) and their association with cardiovascular outcomes.

Clinical staging to guide management of metabolic disorders and their sequelae: a European Atherosclerosis Society consensus statement.

Obesity rates have surged since 1990 worldwide. This rise is paralleled by increases in pathological processes affecting organs such as the heart, liver, and kidneys, here termed systemic metabolic disorders (SMDs). For clinical management of SMD, the European Atherosclerosis Society proposes a pathophysiology-based system comprising three stages: Stage 1, where metabolic abnormalities such as dysfunctional adiposity and dyslipidaemia occur without detectable organ damage; Stage 2, which involves early organ damage manifested as Type 2 diabetes, asymptomatic diastolic dysfunction, metabolic-associated steatohepatitis (MASH), and chronic kidney disease (CKD); and Stage 3, characterized by more advanced organ damage affecting multiple organs.

The CREscendoing promise of HDAC targeting to limit atherosclerosis.

The factors that modulate the inflammatory response in atherosclerosis are not well defined. In this issue of Immunity, Asare et al. examine the impact of a cis-regulatory element (CRE) that controls expression of HDAC9 and find that HDAC9-mediated deacetylation of NLRP3 might be the mechanism by which genetic variants in this conserved CRE influence the inflammation associated with human atherosclerosis.

Roadmap for alleviating the manifestations of ageing in the cardiovascular system.

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Association of clonal haematopoiesis with recurrent venous thromboembolism: A case-control study.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Clonal haematopoiesis (CH) is linked to cardiovascular disease risk, but its potential association with VTE remains poorly understood. We assessed the prevalence of CH in patients with recurrent VTE (n = 107; median age [IQR] 57 [48-63] years, 44.

Extracellular Vesicles as Mediators in Atherosclerotic Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease of the arterial intima, characterized by accumulation of lipoproteins and accompanying inflammation, leading to the formation of plaques that eventually trigger occlusive thrombotic events, such as myocardial infarction and ischemic stroke. Although many aspects of plaque development have been elucidated, the role of extracellular vesicles (EVs), which are lipid bilayer-delimited vesicles released by cells as mediators of intercellular communication, has only recently come into focus of atherosclerosis research. EVs comprise several subtypes that may be differentiated by their size, mode of biogenesis, or surface marker expression and cargo.

Malondialdehyde-specific natural IgM inhibit NETosis triggered by culprit site-derived extracellular vesicles from myocardial infarction patients.

Background And Aims: Neutrophil extracellular traps (NETs) trigger atherothrombosis during acute myocardial infarction (AMI), but mechanisms of induction remain unclear. Levels of extracellular vesicles (EV) carrying oxidation-specific epitopes (OSE), which are targeted by specific natural immunoglobulin M (IgM), are increased at the culprit site in AMI. This study investigated EV as inducers of NETosis and assessed the inhibitory effect of natural anti-OSE-IgM in this process.

Targeting organ-specific mitochondrial dysfunction to improve biological aging.

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function.

TREM2 protects from atherosclerosis by limiting necrotic core formation.

Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications, myocardial infarction and stroke, are the leading cause of mortality worldwide [1], [2]. Recent studies have identified Triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions [3], to be highly expressed in macrophage foam cells in experimental and human atherosclerosis [4]. However, the role of TREM2 in atherosclerosis is not fully known.

Autoimmune diseases and atherosclerotic cardiovascular disease.

Autoimmune diseases are associated with a dramatically increased risk of atherosclerotic cardiovascular disease and its clinical manifestations. The increased risk is consistent with the notion that atherogenesis is modulated by both protective and disease-promoting immune mechanisms. Notably, traditional cardiovascular risk factors such as dyslipidaemia and hypertension alone do not explain the increased risk of cardiovascular disease associated with autoimmune diseases.

Loss of TET2 increases B-1 cell number and IgM production while limiting CDR3 diversity.

Recent studies have demonstrated a role for Ten-Eleven Translocation-2 (TET2), an epigenetic modulator, in regulating germinal center formation and plasma cell differentiation in B-2 cells, yet the role of TET2 in regulating B-1 cells is largely unknown. Here, B-1 cell subset numbers, IgM production, and gene expression were analyzed in mice with global knockout of TET2 compared to wildtype (WT) controls. Results revealed that TET2-KO mice had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow (B-1a) and spleen (B-1b).

Marginal zone B cells produce 'natural' atheroprotective IgM antibodies in a T cell-dependent manner.

Aims: The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of 'poorly differentiated' T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies.

Effects of Tulp4 deficiency on murine embryonic development and adult phenotype.

Genetically engineered mouse models have the potential to unravel fundamental biological processes and provide mechanistic insights into the pathogenesis of human diseases. We have previously observed that germline genetic variation at the TULP4 locus influences clinical characteristics in patients with myeloproliferative neoplasms. To elucidate the role of TULP4 in pathological and physiological processes in vivo, we generated a Tulp4 knockout mouse model.

Mutational landscape of intestinal crypt cells after long-term in vivo exposure to high fat diet.

Obesity is a modifiable risk factor in cancer development, especially for gastrointestinal cancer. While the etiology of colorectal cancer is well characterized by the adenoma-carcinoma sequence, it remains unclear how obesity influences colorectal cancer development. Dietary components of a high fat diet along with obesity have been shown to modulate the cancer risk by perturbing the homeostasis of intestinal stem cells, yet how adiposity impacts the development of genomic instability has not been studied.

Cell-autonomous regulation of complement C3 by factor H limits macrophage efferocytosis and exacerbates atherosclerosis.

Complement factor H (CFH) negatively regulates consumption of complement component 3 (C3), thereby restricting complement activation. Genetic variants in CFH predispose to chronic inflammatory disease. Here, we examined the impact of CFH on atherosclerosis development.