Arteriosclerosis, Thrombosis, and Vascular Biology

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Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by innate and adaptive immunity including humoral immunity. Importantly, antibody alterations achieved by genetic means or active and passive immunization strategies in preclinical studies can improve or aggravate atherosclerosis. Additionally, a wide range of epidemiological data demonstrate not only an association between the total levels of different antibody isotypes but also antibody levels targeting specific antigens with atherosclerotic cardiovascular disease...

BACKGROUND: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models...

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BACKGROUND: Metabolic dysfunction-associated fatty liver disease is a significant risk factor for cardiovascular disease (CVD). This study assesses the association between leisure-time physical activity, sedentary behavior, and CVD risk among patients with metabolic dysfunction-associated fatty liver disease, considering genetic predisposition to CVD. METHODS: This cohort study included 157 794 participants with metabolic dysfunction-associated fatty liver disease from the UK Biobank who were free of CVD at baseline...

BACKGROUND: Lymphatic valves are specialized structures in collecting lymphatic vessels and are crucial for preventing retrograde lymph flow. Mutations in valve-forming genes have been clinically implicated in the pathology of congenital lymphedema. Lymphatic valves form when oscillatory shear stress from lymph flow signals through the PI3K/AKT pathway to promote the transcription of valve-forming genes that trigger the growth and maintenance of lymphatic valves. Conventionally, in many cell types, AKT is phosphorylated at Ser473 by the mTORC2 (mammalian target of rapamycin complex 2)...

BACKGROUND: Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples...

BACKGROUND: HCC-1 (hemofiltrate CC chemokine-1), a CC-type chemokine, exerts function to change intracellular calcium concentration, induce leukocyte, and manipulate enzyme release especially in monocytes. It has been reported that HCC-1 could predict the persistent acute kidney injury or suppress hepatocellular carcinoma by modulating cell cycle and promoting apoptosis, while the effect of HCC-1 on atherosclerosis is poorly understood. Here, we aimed to clarify the function and mechanism of HCC-1 in atherosclerosis and whether it could serve as a novel biomarker for the diagnosis of atherosclerosis...

BACKGROUND: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE. METHODS: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease...

BACKGROUND: In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated...

BACKGROUND: Abdominal aortic aneurysms expand over time and increase the risk of fatal ruptures. To predict expansion, the isolated assessment of 18 F-fluorodeoxyglucose (FDG) and sodium fluoride (NaF) uptake or calcification volume in aneurysms has been investigated with variability in results. We systematically evaluated whether 18 F-FDG and 18 F-NaF uptake was predictive of abdominal aortic aneurysm expansion. METHODS: Seventy-four male Sprague-Dawley rat abdominal aortic aneurysm models were imaged using positron emission tomography-computed tomography with 18 F-FDG and 18 F-NaF at 1, 2, 4, 6, and 8 weeks after CaCl2 or saline stimulation...

Atherosclerosis is a chronic inflammatory disease whose progression is fueled by proinflammatory moieties and limited by anti-inflammatory mediators. Whereas oxidative damage and the generation of oxidation-specific epitopes that act as damage-associated molecular patterns are highly inflammatory, IgM antibodies produced by B-1 and marginal zone B cells counteract unrestricted inflammation by neutralizing and encouraging clearance of these proinflammatory signals. In this review, we focus on describing the identities of IgM-producing B cells in both mice and humans, elaborating the mechanisms underlying IgM production, and discussing the potential strategies to augment the production of atheroprotective IgM...

BACKGROUND: In early atherosclerosis, circulating LDLs (low-density lipoproteins) traverse individual endothelial cells by an active process termed transcytosis. The CANTOS trial treated advanced atherosclerosis using a blocking antibody for IL-1β (interleukin-1β); this significantly reduced cardiovascular events. However, whether IL-1β regulates early disease, particularly LDL transcytosis, remains unknown. METHODS: We used total internal reflection fluorescence microscopy to quantify transcytosis by human coronary artery endothelial cells exposed to IL-1β...

BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated by circulating inflammatory and valve resident endothelial and interstitial cells. The impact of platelets, platelet-derived mediators, and platelet-monocyte interactions on the acceleration of local valvular inflammation and mineralization is presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic valve replacement...

BACKGROUND: Evidence suggests that COVID-19 predisposes to cardiovascular diseases (CVDs). While monocytes/macrophages play a central role in the immunopathogenesis of atherosclerosis, less is known about their immunopathogenic mechanisms that lead to CVDs during COVID-19. Natural killer (NK) cells, which play an intermediary role during pathologies like atherosclerosis, are dysregulated during COVID-19. Here, we sought to investigate altered immune cells and their associations with CVD risk during severe COVID-19...

BACKGROUND: Hyponatremia, frequently observed in patients with chronic kidney disease, is associated with increased cardiovascular morbidity and mortality. Hyponatremia or low osmolality induces oxidative stress and cell death, both of which accelerate vascular calcification (VC), a critical phenotype in patients with chronic kidney disease. Whether hyponatremia or low osmolality plays a role in the pathogenesis of VC is unknown. METHODS: Human vascular smooth muscle cells (VSMCs) and mouse aortic rings were cultured in various osmotic conditions and calcifying medium supplemented with high calcium and phosphate...

BACKGROUND: Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN. METHODS: We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.