Understanding immunometabolism in cardiovascular disease: translating research into practice.

G.D.N. is supported by Progetti di Rilevante Interesse Nazionale (PRIN 2022 7KTSAT), Ricerca Finalizzata, Ministry of Health (RF-2019- 12370896), PNRR Missione 4, (Progetto CN3-National Center for Gene Therapy and Drugs based on RNA Technology), PNRR Missione 4 (Progetto MUSA-Multilayered Urban Sustainability Action), PNRR Missione 6 (PNRR-MAD-2022-12375913), European Commission (EUROPEAID/173691/DD/ACT/XK Nanokos), and European Research Area for Health (ERA4Health; GA No. 101095426 of the EU Horizon Europe Research and Innovation Programme). D.F.J.K. is supported by grants from the Novo Nordisk Foundation (0064142; 0075258); Independent Research Fund Denmark (2034-00136B), Simon Fougner Hartmanns Familiefond (2023-0066), and the University of Southern Denmark. J.V.d.B. was funded by a consortia grant from European Research Area Network on Cardiovascular Diseases (ERA-CVD 2019T108), The Netherlands Heart Foundation senior fellowship (2017T048), and an ENWKlein-1 grant from NWO (OCENW.KLEIN.268). Work in the D.S. laboratory is funded by the CNIC; by MCIN PID2022-137712OB-I00, CPP2021-008310, and CPP2022-009762 MCIN/AEI/10.13039/ 501100011033 Unión Europea NextGenerationEU/PRTR; by Comunidad de Madrid (P2022/BMD-7333 INMUNOVAR-CM); and by ‘la Caixa’ Foundation (LCF/PR/HR23/52430012, LCF/PR/HR22/ 52420019, and LCF/PR/HR20/52400015).S

Uptake of oxLDL and IL-10 production by macrophages requires PAFR and CD36 recruitment into the same lipid rafts

Macrophage interaction with oxidized low-density lipoprotein (oxLDL) leads to its differentiation into foam cells and cytokine production, contributing to atherosclerosis development. In a previous study, we showed that CD36 and the receptor for platelet-activating factor (PAFR) are required for oxLDL to activate gene transcription for cytokines and CD36. Here, we investigated the localization and physical interaction of CD36 and PAFR in macrophages stimulated with oxLDL. We found that blocking CD36 or PAFR decreases oxLDL uptake and IL-10 production. OxLDL induces IL-10 mRNA expression only in HEK293T expressing both receptors (PAFR and CD36). OxLDL does not induce IL-12 production. The lipid rafts disruption by treatment with βCD reduces the oxLDL uptake and IL-10 production. OxLDL induces co-immunoprecipitation of PAFR and CD36 with the constitutive raft protein flotillin-1, and colocalization with the lipid raft-marker GM1-ganglioside. Finally, we found colocalization of PAFR and CD36 in macrophages from human atherosclerotic plaques. Our results show that oxLDL induces the recruitment of PAFR and CD36 into the same lipid rafts, which is important for oxLDL uptake and IL-10 production. This study provided new insights into how oxLDL interact with macrophages and contributing to atherosclerosis development

New trends in globalization of science and engineering education

Three decades ago most research and design were conducted in each country independently. But the world has become quite different since then. Global changes in technology and society changed the concept of an engineer. There is the need for engineers who can work effectively in changing global and technical environments. Less interest has been paid to the globalization of science and technology. This article reviews the stimulus, that impact the engineering profession and gives the recommendations concerning the profession of engineering, the technology and innovation

Highlights from 2022 in EHJ Open.

editorial reviewe

Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice

Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage

Microvesicles in vascular homeostasis and diseases. Position Paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology

Microvesicles are members of the family of extracellular vesicles shed from the plasma membrane of activated or apoptotic cells. Microvesicles were initially characterised by their pro-coagulant activity and described as "microparticles". There is mounting evidence revealing a role for microvesicles in intercellular communication, with particular relevance to hemostasis and vascular biology. Coupled with this, the potential of microvesicles as meaningful biomarkers is under intense investigation. This Position Paper will summarise the current knowledge on the mechanisms of formation and composition of microvesicles of endothelial, platelet, red blood cell and leukocyte origin. This paper will also review and discuss the different methods used for their analysis and quantification, will underline the potential biological roles of these vesicles with respect to vascular homeostasis and thrombosis and define important themes for future research

Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe⁻/⁻ mice

OBJECTIVE: To modulate atherosclerosis by combining subcutaneous immunization with heat shock protein 65 (hsp65) in alum adjuvant and anti-CD45RB monoclonal antibodies (mAb). METHODS: 8 week old Apoe⁻/⁻ mice on normal chow were treated for 12 weeks: group A received hsp65-alum immunization combined with anti-CD45RB mAb, group B hsp65-alum immunization combined with isotype control antibody, and group C mock vaccine combined with isotype control antibody. RESULTS: Unexpectedly, atherosclerotic lesions in the aortic root were significantly reduced in both hsp65-alum immunization groups (A and B) compared with the control group (C). Significantly elevated antibody titers against hsp65 were detected in both groups along with a significant increase in MHC class II expression on B cells. Body weight, total cholesterol and triglyceride levels were not different between groups. Treatment with anti-CD45RB antibody mediated a shift on CD4⁺ T cells from the CD45RB(high) to CD45RB(low) isoform with a relative increase in CD4⁺Foxp3⁺ regulatory T cells (Treg) in an overall reduced T cell pool. Furthermore, anti-CD45RB treatment mediated a transient reduction of peripheral leukocytes and increased IFN-γ and IL-17A plasma levels. CONCLUSIONS: Subcutaneous immunization with hsp65-alum protects Apoe⁻/⁻ mice against progression of early atherosclerosis. Administration of anti-CD45RB antibody provided no incremental benefit to the athero-protective effects of hsp65-alum treatment alone

Role of PPAR-gamma in the Modulation of CD36 and FcgammaRII induced by LDL with Low and High Degrees of Oxidation During the Differentiation of the Monocytic THP-1 Cell Line

Scavenger or Fc gamma receptors are important for capture and clearance of modified LDL particles by monocytes/macrophages. Uptake via scavenger receptors is not regulated by intracellular levels of cholesterol and in consequence, macrophages develop into foam cells in the arterial intima. The levels of scavenger receptor CD36 are increased in atherosclerotic lesions and there is evidence that some components of oxLDL auto-regulate the expression of this receptor. Fc gamma receptor expression is increased in cardiovascular diseases but it is not known weather their expression is regulated by oxLDL. The biological properties of oxLDLs vary depending on the degree of oxidation. In the present study we investigated the effect of LDL particles showing extensive or low oxidation (HoxLDL and LoxLDL) on the expression of CD36 and Fc gamma RII in a human monocytic cell line (THP-1), differentiated or not to macrophage, and the involvement of PPAR gamma. It was found that both forms of oxLDL are able to increase the expression of CD36 and Fc gamma RII and that this effect is dependent on the degree of oxidation and of the stage of cell differentiation ( monocyte or macrophage). We also showed that the increased expression of Fc gamma RII is dependent on PPAR. whereas that of the CD36 is independent of PPAR gamma. Copyright (c) 2008 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto do Milenio de Fluidos Complexos (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Coordena ao de Aperfei oamento de Pessoal de N vel Superior (CAPES

The role of oxidized low density lipoprotein (oxLDL) derived antigens and IgG autoantibodies in coronary artery disease (CAD)

Karolinska Univ Hosp, Ctr Mol Med, Dept Med, Stockholm, SwedenUniv São Paulo, Inst Biomed Sci, São Paulo, BrazilUnifesp, São Paulo, BrazilSante Pazzanese, Inst Cardiol, São Paulo, BrazilUnifesp, São Paulo, BrazilWeb of Scienc