Inherited Dyslipidemic Splenomegaly: A Genetic Macrophage Storage Disorder Caused by Disruptive Apolipoprotein E (APOE) Variants DOI Open Access
Elise A. Ferreira, Machteld M. Oud, Saskia N. van der Crabben

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(3), P. 289 - 289

Published: Feb. 27, 2025

Background: Persistent splenomegaly, often an incidental finding, can originate from a number of inherited metabolic disorders (IMDs). Variants APOE are primarily known as risk factors in terms cardiovascular disease; however, severe dysfunction result disease phenotype with considerable overlap lysosomal storage (LSDs), including splenomegaly and gross elevation N-palmitoyl-O-phosphocholine-serine (PPCS). Methods: A case study (deep phenotyping, genetic FACS analysis) literature was conducted. Results: The index patient, family history early-onset disease, presented splenic infarctions grossly enlarged spleen. identified cause homozygosity for two variants (c.604C>T, p.(Arg202Cys) c.512G>A, p.(Gly171Asp); ε1/ε1), resulting macrophage resembling LSD that also present the brother patient. analysis circulating monocytes showed increased lipid content expression activation markers (CD11b, CCR2, CD36). This activated state enhances lipoprotein intake, which eventually converts these monocytes/macrophages into foam cells, accumulating tissues (e.g., spleen vascular wall). search seven individuals caused by (deletion leucine at position 167). combined data all patients male gender, splenectomy obesity potential modifiers determining severity (i.e., degree triglyceride increase plasma and/or size). Symptoms (partially) reversible lipid-lowering medication energy restricted diets is contra-indicated. Conclusions: Inherited dyslipidemic disruptive should be included differential diagnoses unexplained abnormal profiles. profile consistent dysbetalipoproteinemia diagnostic biomarker this IMD.

Language: Английский

Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration DOI Creative Commons
Alejandra P. Garza, Lorena Morton, Éva Pállinger

et al.

Brain Behavior & Immunity - Health, Journal Year: 2023, Volume and Issue: 28, P. 100597 - 100597

Published: Jan. 29, 2023

Tobacco smoking is strongly linked to vascular damage contributing the development of hypertension, atherosclerosis, as well increasing risk for neurodegeneration. Still, involvement innate immune system in upon chronic tobacco use before onset clinical symptoms not fully characterized. Our data provide evidence that a single acute exposure elicits secretion extracellular vesicles expressing CD105 and CD49e from endothelial cells, granting further recognition early preclinical biomarkers damage. Furthermore, we investigated effects on healthy asymptomatic smokers compared never-smokers, focusing system. reveal distinct landscape representative stages clinically smokers, related diseases develop. These results indicate dysregulated immuno-vascular axis are otherwise considered individuals. The alterations characterized by increased CD36 expression blood monocyte subsets, neutrophilia plasma IL-18 reduced levels IL-33, IL-10 IL-8. Additionally, circulating BDNF elevated sTREM2, which associated with neurodegeneration, suggest considerable impact CNS function findings profound insight into initial ongoing potential neurodegenerative disorders, specifically cerebrovascular dysfunction dementia.

Language: Английский

Citations

22
Injectable liposomal docosahexaenoic acid alleviates atherosclerosis progression and enhances plaque stability DOI
Suet Yen Chong, Xiaoyuan Wang,

Louis van Bloois

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 360, P. 344 - 364

Published: July 7, 2023

Language: Английский

Citations

19
The role of systemic inflammation and oxidative stress in the association of particulate air pollution metal content and early cardiovascular damage: A panel study in healthy college students DOI
Lei Zhang, Bo Fang, Haotian Wang

et al.

Environmental Pollution, Journal Year: 2023, Volume and Issue: 323, P. 121345 - 121345

Published: Feb. 23, 2023

Language: Английский

Citations

17
Short-chain fatty acids are potential goalkeepers of atherosclerosis DOI Creative Commons
Yu Feng, Danyan Xu

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 13, 2023

Short-chain fatty acids (SCFAs) are metabolites produced by gut bacteria and play a crucial role in various inflammatory diseases. Increasing evidence suggests that SCFAs can improve the occurrence progression of atherosclerosis. However, molecular mechanisms through which regulate development atherosclerosis have not been fully elucidated. This review provides an overview research progress on regarding their impact risk factors pathogenesis associated with atherosclerosis, specific focus interactions endothelium immune cells. These encompass inflammation oxidative stress endothelial cells, migration monocytes/macrophages, lipid metabolism macrophages, proliferation smooth muscle differentiation Treg Nevertheless, current body is insufficient to comprehensively understand full spectrum SCFAs’ action. Therefore, further in-depth investigations imperative establish solid theoretical foundation for clinical therapeutics this context.

Language: Английский

Citations

16
Genetic Markers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease DOI Creative Commons

Sangeetha Perumalsamy,

Hasniza Zaman Huri, Bashar Mudhaffar Abdullah

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(3), P. 427 - 427

Published: March 14, 2023

Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion on a background of resistance (IR). IR and T2DM are associated with atherosclerotic coronary artery disease (CAD). The mechanisms atherosclerosis known to share similar genetic environmental roots. Endothelial dysfunction (ED) detected at the earliest stages might be origin progression. ED influences pro-inflammatory cytokines their encoding genes. genes single nucleotide polymorphisms (SNPs) act as potential markers atherosclerosis. This review focuses link between IR, T2DM, atherosclerosis, CAD, CHI3L1, CD36, LEPR, RETN, IL-18, RBP-4, RARRES2

Language: Английский

Citations

15
Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis DOI Creative Commons
Anne Nègre‐Salvayre,

Robert Salvayre

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 232 - 232

Published: Feb. 14, 2024

Atherosclerosis is a multifactorial disease of medium and large arteries, characterized by the presence lipid-rich plaques lining intima over time. It main cause cardiovascular diseases death worldwide. Redox imbalance lipid peroxidation could play key roles in atherosclerosis promoting bundle responses, including endothelial activation, inflammation, foam cell formation. The oxidation polyunsaturated fatty acids generates various products such as reactive carbonyl species (RCS), 4-hydroxy alkenals, malondialdehyde, acrolein. RCS covalently bind to nucleophilic groups nucleic acids, phospholipids, proteins, modifying their structure activity leading progressive dysfunction. Protein lipoxidation non-enzymatic post-translational modification proteins RCS. Low-density lipoprotein (LDL) apolipoprotein B (apoB) major role Moreover, oxidized LDLs are source RCS, which form adducts on huge number depending oxidative stress intensity, nature targets, availability detoxifying systems. Many systems affected lipoxidation, extracellular matrix components, membranes, cytoplasmic cytoskeletal transcription factors, other components. mechanisms involved lipoxidation-induced vascular dysfunction not fully elucidated. In this review, we focus protein during atherogenesis.

Language: Английский

Citations

5
Mechanism of efferocytosis in atherosclerosis DOI

Li-Xia Shu,

Liu-li Cao,

Xin Guo

et al.

Journal of Molecular Medicine, Journal Year: 2024, Volume and Issue: 102(7), P. 831 - 840

Published: May 10, 2024

Language: Английский

Citations

5
Atherosclerosis: Immunopathogenesis and Strategies for Immunotherapy DOI
Jorge H. Tabares-Guevara, Janny A. Villa-Pulgarín, Juan C. Hernández

et al.

Immunotherapy, Journal Year: 2021, Volume and Issue: 13(14), P. 1231 - 1244

Published: Aug. 12, 2021

Atherosclerosis, a chronic inflammatory condition in which atheroma accumulates within the intima of arterial wall, is life-threatening manifestation cardiovascular disease, due to rupture, luminal narrowing and thrombosis. Current knowledge role protective immune response atherosclerotic lesions has provided promising opportunities develop new immunotherapeutic strategies. In particular, Tregs exert an atheroprotective by releasing anti-inflammatory cytokines (IL-10/TGF-β) suppressing autoreactive T lymphocytes. vivo animal experiments have shown that this can be achieved developing vaccines stimulate immunological tolerance antigens. Here, we present overview current proatherogenic response, discuss strategies currently used as immunoregulatory therapy.

Language: Английский

Citations

32
High fructose diet: A risk factor for immune system dysregulation DOI
Hao Cheng,

Jingyang Zhou,

Yutong Sun

et al.

Human Immunology, Journal Year: 2022, Volume and Issue: 83(6), P. 538 - 546

Published: April 9, 2022

Language: Английский

Citations

22
Sustained Proinflammatory Effects of Hypoglycemia in People With Type 2 Diabetes and in People Without Diabetes DOI Open Access
Clementine E. M. Verhulst, Julia I. P. van Heck, Therese W. Fabricius

et al.

Diabetes, Journal Year: 2022, Volume and Issue: 71(12), P. 2716 - 2727

Published: July 18, 2022

Iatrogenic hypoglycemia activates the immune system and is associated with an increased risk for atherosclerotic disease. We determined acute long-term effects of insulin-induced on inflammatory markers in humans or without type 2 diabetes. A total 15 adults diabetes 16 matched control subjects (17 men 14 women, age 59.6 ± 7.1 years, BMI 28.5 4.3 kg/m2) underwent a hyperinsulinemic-euglycemic (5.31 0.32 mmol/L) hypoglycemic (2.80 0.12 glucose clamp. Blood was drawn during euglycemia 1, 3, 7 days later to determine circulating cell composition, function, proteins. In response hypoglycemia, absolute numbers lymphocytes monocytes significantly remained elevated 1 week. The proportion CD16+ increased, CD14+ decreased, which sustained week people During ex vivo stimulated released more tumor necrosis factor-α interleukin 1β, less 10, particularly hs-CRP 25 proteins remaining after hypoglycemia. While levels at differed, responses were broadly similar conclude that induces proinflammatory cellular protein level subjects.

Language: Английский

Citations

20