Cardiovascular risk in patients with type 2 diabetes is associated with alteration of blood monocyte phenotype and plasma metabolome
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PROVIDER: PRJNA828266 | ENA |
REPOSITORIES: ENA
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Project description:To gain insight into the relationship between circulating monocytes and cardiovascular risk (CV) progression in patients with type 2 diabetes (T2D), we collected blood monocytes (CD14 positive selection) from 92 people with type 2 diabetes and coronary artery calcium score (CAC-score). Gene expression profiles of circulating monocytes were assessed by RNA sequencing.
2024-01-08 | GSE201087 | GEO
Project description:Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States
| PRJNA1260402 | ENA
Project description:Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized. We utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to describe the comprehensive transcriptional and phenotypic landscape of 437,126 monocytes. This high-dimensional multimodal approach identified vast phenotypic diversity and functionally distinct subsets, including IFN-responsive, MHCIIhi, monocyte-platelet aggregates, as well as non-classical, sand several subpopulations of classical monocytes. Using flow cytometry, we validated the existence of MHCII+CD275+ MHCIIhi, CD42b+ monocyte-platelet aggregates, CD16+CD99- non-classical monocytes, and CD99+ classical monocytes. Each subpopulation exhibited unique characteristics, developmental trajectories, transcriptional regulation, and tissue distribution. In addition, alterations associated with cardiovascular disease (CVD) risk factors, including race, smoking, and hyperlipidemia were identified. Moreover, the effect of hyperlipidemia was recapitulated in mouse models of elevated cholesterol. This integrative and cross-species comparative analysis provides a new perspective on comparison of alterations in monocytes in pathological conditions and offers insights into monocyte-driven mechanisms in CVD and the potential for monocyte subpopulation targeted therapies.
2025-05-08 | GSE296624 | GEO
Project description:Both clinical and laboratory studies have shown that monocyte chemotactic protein-1 (MCP-1) is involved in cancer spread. To understand the role of MCP-1 in metabolism in the presence of metastasis, we conducted an untargeted metabolomic analysis of primary metabolism on plasma collected from a study showing that MCP-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma (LLC) to the lungs in mice fed a high-fat diet (HFD). In a 2 × 2 design, wild-type (WT) or Mcp-1 knockout (Mcp-1 -/-) mice maintained on the AIN93G standard diet or HFD were subcutaneously injected with LLC cells to induce lung metastasis. We identified 87 metabolites for metabolomic analysis from this study. Amino acid metabolism was altered considerably in the presence of LLC metastases with the aminoacyl-tRNA biosynthesis pathways as the leading pathway altered. The HFD modified lipid and energy metabolism, evidenced by lower contents of arachidonic acid, cholesterol, and long-chain saturated fatty acids and higher contents of glucose and pyruvic acid in mice fed the HFD. These findings were supported by network analysis showing alterations in fatty acid synthesis and glycolysis/gluconeogenesis pathways between the 2 diets. Furthermore, elevations of the citrate cycle intermediates (citric acid, fumaric acid, isocitric acid, and succinic acid) and glyceric acid in Mcp-1 -/- mice, regardless of diet, suggest the involvement of MCP-1 in mitochondrial energy metabolism during LLC metastasis. The present study demonstrates that MCP-1 deficiency and the HFD altered plasma metabolome in mice bearing LLC metastases. These findings can be useful in understanding the impact of obesity on prevention and treatment of cancer metastasis.
| S-EPMC9358346 | biostudies-literature
Project description:Extracellular vesicles (EV) convey biological messages through their cargoes. Herein we focus on monocyte/platelet aggregates characteristic of several cardiovascular diseases with an analysis of monocyte-derived EV (mEVs) effects on the atherosclerotic plaque. Monocyte preparations were stimulated with TNF-α in presence or absence of prostacyclin and EVs isolated via centrifugation. EV physical characteristics were determined by Nanoparticle Tracking analysis while surface profile was analysed using imaging flow cytometry. Atherosclerotic plaques from 5 patients undergoing endarterectomy were cultured with or without mEVs. Cytokines and proteins released in the culture media were measured by multiplex ELISA and mass spectrometry. Proteomic of mEVs prepared in different incubation settings was also conducted. Monocyte isolation yielded ~80% platelet-monocyte aggregates. TNF-α stimulation produced CD14+ EVs as well as a subset bearing the CD41 marker for platelets (CD14+/CD41+). Prostacyclin addition did not modulate monocyte/platelet aggregates, but impacted on mEV numbers. Addition of TNF-α mEVs on atherosclerotic plaque fragments impacted on general protein release (19 upregulated and 7 downregulated) and elevated cytokine release. mEVs generated by TNF-α and prostacyclin produced minimal changes on plaque reactivity. Proteomic analysis of mEVs revealed a distinctive composition when the cell preparation was activated with TNF-α alone or with prostacyclin. In conclusion, mEVs activate the atherosclerotic plaque. Attenuating platelet activation has an effect on EV composition with downstream modulation of their pro-inflammatory actions. EV heterogeneity reflects the mode of activation of the cell of origin and may differently contribute to the development and progression of atherosclerosis.
2021-09-08 | PXD014325 | Pride
Project description:Extracellular vesicles (EV) are cell-secreted, nano-sized membrane particles with various molecular cargo, including metabolites, proteins and nucleic acids [1] . EVs are involved in various physiological and pathological functions, including that of the myocardium [2] , such as cardiac stress adaptation mechanisms [3] . Metabolic co-morbidities can ameliorate the innate stress response of the heart [4], [5] . Furthermore, one of the most common metabolic co-morbidities, type-II diabetes, can inhibit EV- mediated cardioprotection [6] . EVs of high-fat fed animals can also exacerbate ischemic cardiac damage and induce cell death of cardiomyocytes (CM) [7], [8] . Therefore, metabolic diseases might interfere with the effect of cardiac EVs by various mechanisms. However, as of now, little is known about the effect of hypercholesterolemia (HC) on cardiovascular EV communication. Analyzing EVs of the circulation might lead to novel diagnostic tools and to better understanding of disease conditions. As of now it is evidenced that circulating EV number is increased in metabolic diseases [9]–[11] , including familiar hypercholesterolemia [12], [13] , in which their amount is associated with the risk of cardiovascular diseases [14], [15] as well. However, to understand the biological role of EV-related changes in cardiometabolic diseases, characterization of EV composition is needed. The main molecular constituents of EVs are membrane lipids and other metabolites, intravesicular and transmembrane proteins and nucleotides. Change in any of these constituents may result in an altered biological response. Barrachina et. al. has analyzed the dysregulated protein composition of circulating EVs in obesity [16] and in a similar study, miRNA cargo of EVs from obese patients was analyzed, as well [17] , however, it has not been assessed if HC alters EV metabolome, thus, function. EVs contribute to response to various stresses in the myocardium [18] , but as of now, we do not know HC influences EV release of CMs. One of the major effects of HC is cardiac- and systemic inflammation [19] . Earlier studies showed in various disease conditions, such as angiotensin II-induced hypertrophy, that CM EVs activate monocytes, thereby contribute to inflammation [20], [21] . In contrast, in hypoxic conditions, EVs promote macrophage polarization to the reparative M2 phenotype [22], [23] . Thus, we hypothesized that CM EVs might play a role in HC-induced cardiac inflammation. In this study, we aimed to analyze how HC affects the metabolic composition of EVs and how HC modifies CM EV communication. Therefore, we have analyzed the metabolome of circulating EVs of HC- fed rats and compared the identified changes to the plasma metabolome. In addition, for the first time, we assessed how HC affects the biophysical and biochemical properties of CM EVs and we analyzed their role in immune activation.
2024-06-16 | PXD044594 | Pride
Project description:Interventions: monocyte/neutrophil apheresis
non monocyte/neutrophil apheresis
Primary outcome(s): Evaluation neutrophil function of patients at high risk for postoperative infection treated with monocyte/neutrophil apheresis
Study Design: Parallel Non-randomized
| 2627605 | ecrin-mdr-crc
Project description:Interventions: multiple monocyte/neutrophil apheresis
non monocyte/neutrophil apheresis
Primary outcome(s): Evaluation neutrophil function of patients at high risk for postoperative infection treated with monocyte/neutrophil apheresis
Study Design: Parallel Non-randomized
| 2628620 | ecrin-mdr-crc
Project description:AimsTo investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk.Methods and resultsOur primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses' Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28-0.37 between the signature and MEDAS; P = 3 × 10-35 to 4 × 10-118). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: hazard ratio [HR] per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001).ConclusionsWe identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.
| S-EPMC7377580 | biostudies-literature
Project description:Action to Control Cardiovascular Risk in Diabetes (ACCORD-BioLINCC)
| PRJNA1075471 | ENA