Biology subjects

Masson, D.

Publications and source records attributed to Masson, D..

4 recordsLinked to original sources

bioRxiv2025

REGULATION OF HDL DYSFUNCTIONALITY BY PHOSPHATIDYLETHANOLAMINE LINKS POLY-UNSATURATED FATTY ACIDS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASES

AimsLow plasma high-density lipoprotein (HDL)-cholesterol levels are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD), potentially reflecting impaired antiatherogenic HDL functions. These latter are strongly influenced by the HDL phospholipidome, which is frequently altered in ASCVD patients. Several studies reported that plasma levels of phosphatidylethanolamine (PE) species, particularly PE (36:5), were positively associated with ASCVD, but the underlying mechanisms remain unclear. Plasma PE (36:5) exists as eicosapentaenoic (EPA)-PE and arachidonic acid (ARA)-PE, with the latter predominating in ASCVD. This study investigated whether the association of PE (36:5) with ASCVD might result from an impairment of the antiatherogenic functions of HDL. Methods and ResultsTotal PE and PE (36:5) content of large HDL isolated from 86 women with metabolic syndrome was positively associated with carotid intima-media thickness in multivariate regression analysis adjusted for traditional risk factors. In TgCETP x Ldlr-/- mice fed a high-cholesterol diet, the atherosclerotic plaque size was greater when reconstituted HDL (rHDL) containing ARA-PE was injected retro-orbitally, compared with injection of control rHDL containing only phosphatidylcholine (PC). In vitro, PE rHDL showed reduced cholesterol efflux capacity and impaired anti-inflammatory activity in THP-1 macrophages, together with diminished anti-oxidative activity against LDL oxidation compared to control rHDL. Strikingly, ARA-PE rHDL profoundly weakened of the HDL functions, while EPA-PE counteracted the ARA-PE-induced dysfunction and potentiated the functionality of rHDL. ConclusionThis study reveals a causal link between PE species, particularly ARA-PE, and HDL dysfunction, contributing to atherosclerosis. EPA-PE can restore HDL function, supporting the therapeutic potential of EPA reducing ASCVD risk.

cell biology↗

bioRxiv2024

CD226+ adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism.

Macrophages are innate immune cells present in all tissues, in which they participate in immune responses and maintenance of tissue homeostasis. They develop either from embryonic precursors or from circulating monocytes, and their origin impacts their functions. We previously observed robust recruitment of monocytes to brown adipose tissue in which they could differentiation into two distinct macrophage subsets identifiable by CD206 or CD226 expression. In the present study, we investigated monocyte differentiation pathways in brown adipose tissue and the function of monocyte-derived macrophages. Fate mapping analysis revealed a low contribution of GMP- and a high contribution of MDP-derived monocytes to the CD226high macrophage subset. Importantly, adoptive transfer experiments demonstrate that MDP- but not GMP-derived monocytes are pre-conditioned to give rise to CD226high macrophages. We found that MDP-derived CD226high macrophages were also present in other tissues including peritoneal cavity, adrenal glands and all adipose depots. CD226high macrophages were regulated by both GM-CSF and CSF1R. Genetic depletion of CD226high macrophages caused increased BAT and plasma triglyceride content. We thus identify CD226high MDP-derived macrophages as a new myeloid cell type conserved across tissues and tied to lipid metabolism homeostasis.

immunology↗

bioRxiv2023

Atheroma plaque microenvironment stimulates kynurenine production by macrophages to induce endothelial adhesion molecules in the context of atherogenesis

Cardiovascular diseases, including atherosclerosis, are major causes of morbidity and mortality worldwide. Here, we investigate the role of the kynurenine pathway (KP) in macrophages in the context of atheroma plaque microenvironment and its impact on atherogenesis. Using an in vitro model of primary human macrophages, we observed that exposure to plaque homogenates induces a marked increase in the early steps of the KP which impacts on kynurenine production. This was confirmed by immunostaining on human plaque of carotid arteries. Further investigation into the underlying molecular mechanisms revealed that LXR signaling contributes to this plaque microenvironment-induced KP activation. We showed that kynurenine released from macrophages affected endothelial cells, leading to increased expression of ICAM-1 and VCAM-1 in an AhR-dependent manner. Consistently with the proatherogenic effects, in a cohort of atherosclerotic patients, we observed higher levels of plasma kynurenine in patients with lower extremity arterial disease. In line with the results of in vitro investigations, the plasma kynurenine levels were associated plaque oxysterol content. Using a multiple logistic regression model, we showed that plasma kynurenine was independently associated with lower extremity arterial disease in atherosclerotic patients. Altogether, our data indicate that the activation of KP in macrophages in the context of atheroma plaque is partially mediated by LXR axis and leads to the release of kynurenine. This, in turn, contributes to the exacerbation of both local and peripheral atherosclerosis particularly through the activation of endothelial cells.

immunology↗

bioRxiv2017

Response of oriental xerophytes to the occidental industrial revolution

Since the Industrial Revolution, human activities have contributed substantially to climate change, by adding CO2 to the atmosphere, especially since the mid-20th century (the \"Great Acceleration\"). Climatic change does not have the same impact on different regions of the Earth, neither in the recorded past, nor in models of the future. Therefore, to anticipate on these changes, we need to understand and be able to predict the possible responses of the different regional vegetations of the world to these changes, and most significantly to increased drought conditions. The aim of this study is to understand the response of the xerophytes of the immense oriental Irano-Turanian bioregion to post-industrial global warming and to compare it with the response of the xerophytes of the neighbouring occidental Mediterranean bioregion. We measured stomata index and stomata density from 83 herbarium sheets (coll. 1821-2014) from species of the non-succulent xerophyte, Haplophyllum. We tested for differences before and after the \"Great Acceleration\" in both bioregions. SI decreased in the occidental species (significant only for abaxial leaf side), whereas SI significantly increased in the oriental species (both sides). We suggest that changes in both occidental and oriental species are linked to atmospheric CO2 due to the different constraints that act on their growth. In light-limited occidental species, atmospheric CO2 caused the stomata index decrease, whereas in the predominantly water-limited oriental species, increased drought stress and temperature (climatic change) caused stomata index increase. In conclusion, we propose that whereas atmospheric CO2 directly caused a decrease in stomata index in occidental xerophytes, it indirectly caused an increase in stomata index in oriental xerophytes via climate change (increase in aridity, drought stress, and temperature). This study highlights the considerable potential of research based on historical herbarium collections to answer ecological questions, especially regarding climatic change.

plant biology↗