| 1. |
- Amoedo-Leite, Catarina, et al.
(author)
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Macrophages behave like mural cells to promote healing of ischemic muscle injury
- 2024
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In: NATURE CARDIOVASCULAR RESEARCH. - : Springer Nature. - 2731-0590. ; 3:6, s. 625-626
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Journal article (peer-reviewed)abstract
- We discover a function of innate immune cells that is important for healing injury: macrophages adopt mural cell roles that are important for restoring blood vessel function and perfusion.
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| 2. |
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| 3. |
- Claesson-Welsh, Lena, et al.
(author)
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Tyrosine-protein kinase Yes is essential in vascular barrier dynamics
- 2022
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In: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590. ; 1:12, s. 1136-1137
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Journal article (other academic/artistic)abstract
- Endothelial cell-cell contacts in blood vessels constitute a barrier to the flux of molecules and cells from blood to tissues. We identified the tyrosine-protein kinase Yes as the principal regulator of collective endothelial cell migration and vascular barrier dynamics, a finding that opens avenues for future therapeutic development.
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| 4. |
- Dib, Lea, et al.
(author)
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Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications
- 2023
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In: Nature Cardiovascular Research. - 2731-0590. ; 2:7, s. 656-672
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Journal article (peer-reviewed)abstract
- The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse cardiovascular outcomes. Atherosclerosis, a major underlying cause of cardiovascular disease, is conceptualized as lipid-driven inflammation in which macrophages play a nonredundant role. However, evidence emerging so far from single-cell atlases suggests a dichotomy between lipid-associated and inflammatory macrophage states. Here, we present an inclusive reference atlas of human intraplaque immune cell communities. Combining single-cell RNA sequencing (scRNA-seq) of human surgical carotid endarterectomies in a discovery cohort with bulk RNA-seq and immunohistochemistry in a validation cohort (the Carotid Plaque Imaging Project), we reveal the existence of PLIN2hi/TREM1hi macrophages as a Toll-like receptor (TLR)-dependent inflammatory lipid-associated macrophage state linked to cerebrovascular events. Our study shifts the current paradigm of lipid-driven inflammation by providing biological evidence for a pathogenic macrophage transition to an inflammatory lipid-associated phenotype and for its targeting as a new treatment strategy for cardiovascular disease.
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| 5. |
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| 6. |
- Fernandez-Chacon, Macarena, et al.
(author)
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Incongruence between transcriptional and vascular pathophysiological cell states
- 2023
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In: NATURE CARDIOVASCULAR RESEARCH. - : SPRINGERNATURE. - 2731-0590. ; 2:6, s. 530-549
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Journal article (peer-reviewed)abstract
- The Notch pathway is a major regulator of endothelial transcriptional specification. Targeting the Notch receptors or Delta-like ligand 4 (Dll4) dysregulates angiogenesis. Here, by analyzing single and compound genetic mutants for all Notch signaling members, we find significant differences in the way ligands and receptors regulate liver vascular homeostasis. Loss of Notch receptors caused endothelial hypermitogenic cell-cycle arrest and senescence. Conversely, Dll4 loss triggered a strong Myc-driven transcriptional switch inducing endothelial proliferation and the tip-cell state. Myc loss suppressed the induction of angiogenesis in the absence of Dll4, without preventing the vascular enlargement and organ pathology. Similarly, inhibition of other pro-angiogenic pathways, including MAPK/ERK and mTOR, had no effect on the vascular expansion induced by Dll4 loss; however, anti-VEGFA treatment prevented it without fully suppressing the transcriptional and metabolic programs. This study shows incongruence between single-cell transcriptional states, vascular phenotypes and related pathophysiology. Our findings also suggest that the vascular structure abnormalization, rather than neoplasms, causes the reported anti-Dll4 antibody toxicity. Fernandez-Chacon et al. use imaging and scRNA-seq after targeting multiple Notch genes and angiogenic signaling pathways to find that the function of these pathways in vascular pathophysiology cannot be predicted by assessing transcriptional states.
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| 7. |
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| 8. |
- Guillamat-Prats, R, et al.
(author)
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GPR55 in B cells limits atherosclerosis development and regulates plasma cell maturation
- 2022
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In: Nature cardiovascular research. - : Springer Science and Business Media LLC. - 2731-0590. ; 1, s. 1056-1071
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Journal article (peer-reviewed)abstract
- Dissecting the pathways regulating the adaptive immune response in atherosclerosis is of particular therapeutic interest. Here we report that the lipid G-protein-coupled receptor GPR55 is highly expressed by splenic plasma cells (PCs), upregulated in mouse spleens during atherogenesis and human unstable or ruptured compared to stable plaques.Gpr55-deficient mice developed larger atherosclerotic plaques with increased necrotic core size compared to their corresponding controls. Lack of GPR55 hyperactivated B cells, disturbed PC maturation and resulted in IgG overproduction. B-cell-specificGpr55depletion or adoptive transfer ofGpr55-deficient B cells was sufficient to promote plaque development and elevated IgG titers. In vitro, the endogenous GPR55 ligand lysophsophatidylinositol (LPI) enhanced PC proliferation, whereas GPR55 antagonism blocked PC maturation and increased their mitochondrial content. Collectively, these discoveries provide previously undefined evidence for GPR55 in B cells as a key modulator of the adaptive immune response in atherosclerosis.
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| 9. |
- Gustafsson, Stefan, et al.
(author)
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Markers of imminent myocardial infarction
- 2024
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In: Nature Cardiovascular Research. - : Springer Nature. - 2731-0590.
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Journal article (peer-reviewed)abstract
- Myocardial infarction is a leading cause of death globally but is notoriously difficult to predict. We aimed to identify biomarkers of an imminent first myocardial infarction and design relevant prediction models. Here, we constructed a new case–cohort consortium of 2,018 persons without prior cardiovascular disease from six European cohorts, among whom 420 developed a first myocardial infarction within 6 months after the baseline blood draw. We analyzed 817 proteins and 1,025 metabolites in biobanked blood and 16 clinical variables. Forty-eight proteins, 43 metabolites, age, sex and systolic blood pressure were associated with the risk of an imminent first myocardial infarction. Brain natriuretic peptide was most consistently associated with the risk of imminent myocardial infarction. Using clinically readily available variables, we devised a prediction model for an imminent first myocardial infarction for clinical use in the general population, with good discriminatory performance and potential for motivating primary prevention efforts.
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