Sténose carotidienne athéromateuse récemment symptomatique (à la recherche de marqueurs de l'inflammation et d'activation plaquettaire)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Nouveaux biomarqueurs de la maladie coronaire, IL-6, Il-10, LDL oxidées , MMP-2, MMP-9, sICAM-1, sICAM-3, sUPAR, sCD40L and MPO (valeur diagnostique pronostique à 6 mois dans le syndrome coronaire aiguë sans lésion angiocoronographique, avec exploration échographique endocoronaire, à propos de 31 patients)

The aim of our study is to evaluate diagnostic and/or prognostic value of biological markers implicated in atherogenesis or atherosclerotic lesion progression, in patients with acute coronary syndrome with troponin elevation, without angiographic lesion and initial and after 6-month follow-up endocoronary echographic measurements (IVUS). 31 patients were included and 10 biomarkers (IL-6, Il-10, oxidized LDL, MMP-2, MMP-9, sICAM-1, sICAM-3, sUPAR, sCD40L and MPO) were retrospectively measured on blood samples collected after hospital admission (M1) and after 6 months (M6). 13 patients presented an event during follow-up: angioplasty based on IVUS ( 4 patients at M1 and 4 patients after M6) and clinic events (5 patients). 3 blood samples can't be analysed at M6. Some markers seem to have an interest to improve coronary disease's therapeutic strategy, in complement of usual biological explorationTOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Signalisation mitogène des agents pro-athérogènes, implication de la voie béta-caténine

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Physical activity and odds of coronary heart disease among Lebanese women

Abstract Background It is known that physical activity (PA) is protective against cardiovascular morbidity and mortality. However, few studies have examined the association between PA, sedentary lifestyle and coronary heart disease (CHD) in women. This case–control study investigates the relationship between PA and sedentary behavior on CHD odds in Lebanese women over forty. Methods One thousand five hundred selected Lebanese women (300 cases and 1200 controls) were included between 2018–2019. Cases were hospitalized women newly diagnosed with CHD, whereas the control groups were free of any heart diseases. Data on socio-demographic, lifestyle, cardiovascular factors, PA and sedentary lifestyle were collected. Multivariate logistic regressions, adjusted for covariates, were performed to investigate the association of PA domains and sedentary behavior with CHD. Results A sedentary lifestyle combined with low activity levels increased the odds of CHD. Among cases, 46.7% participated in moderate or vigorous PA against almost 60.3% of controls. 36.3% of coronary patients had more than 10 h/day of sedentary time, with a positive correlation with CHD (adjusted OR: 1.533, 95%CI: 1.046–2.247). Conversely, moderate and high levels (respectively 600–3000 and ≥ 3000 metabolic equivalents [MET]-minutes/week) of domestic/garden PA revealed lower CHD odds (OR: 0.566, 95%CI: 0.396–0.808 and 0.193, 0.065–0.578 respectively). The detrimental influence of sedentary lifestyle appeared to be significantly reversed by weekly moderate PA, especially as weekly sedentary time was less (OR: 0.616, 95%CI: 0.427–0.888/ 6 to10h of sedentary time and OR: 0.537, 95% CI: 0.37–0.779/ ≤ 6 h), and except sedentary time exceeding 10 h daily. Two PA patterns revealed lower CHD odds: transport-related and domestic/garden PA, as early as low amount, even after adjustment for possible confounders. Conclusion The current study highlights the importance of combating sedentary behaviors and engaging in regular, easily accessible PA to reduce the odds of coronary disease among aging women. Therefore, better information regarding the benefits of physical activities such as transportation-related activities or gardening would be helpful in enhancing the prevention of CHD in aging women

Intestinal cholesterol transport proteins: an update and beyond.

International audiencePURPOSE OF REVIEW: Various studies have delineated the causal role of dietary cholesterol in atherogenesis. Strategies have thus been developed to minimize cholesterol absorption, and cholesterol transport proteins found at the apical membrane of enterocytes have been extensively investigated. This review focuses on recent progress related to various brush-border proteins that are potentially involved in alimentary cholesterol transport. RECENT FINDINGS: Molecular mechanisms responsible for dietary cholesterol and plant sterol uptake have not been completely defined. Growing evidence, however, supports the concept that several proteins are involved in mediating intestinal cholesterol transport, including SR-BI, NPC1L1, CD36, aminopeptidase N, P-glycoprotein, and the caveolin-1/annexin-2 heterocomplex. Other ABC family members (ABCA1 and ABCG5/ABCG8) act as efflux pumps favoring cholesterol export out of absorptive cells into the lumen or basolateral compartment. Several of these cholesterol carriers influence intracellular cholesterol homeostasis and are controlled by transcription factors, including RXR, LXR, SREBP-2 and PPARalpha. The lack of responsiveness of NPC1L1-deficient mice to ezetimibe suggests that NPC1L1 is likely to be the principal target of this cholesterol-lowering drug. SUMMARY: The understanding of the role, genetic regulation and coordinated function of proteins mediating intestinal cholesterol transport may lead to novel ways of treating cardiovascular disease

Integrin alpha(v)beta(3), metalloproteinases, and sphingomyelinase-2 mediate urokinase mitogenic effect.

International audiencePlasminogen activators are implicated in the pathogenesis of several diseases such as inflammatory diseases and cancer. Beside their serine-protease activity, these agents trigger signaling pathways involved in cell migration, adhesion and proliferation. We previously reported a role for the sphingolipid pathway in the mitogenic effect of plasminogen activators, but the signaling mechanisms involved in neutral sphingomyelinase-2 (NSMase-2) activation (the first step of the sphingolipid pathway) are poorly known. This study was carried out to investigate how urokinase plasminogen activator (uPA) activates NSMase-2. We report that uPA, as well as its catalytically inactive N-amino fragment ATF, triggers the sequential activation of MMP-2, NSMase-2 and ERK1/2 in ECV304 cells that are required for uPA-induced ECV304 proliferation, as assessed by the inhibitory effect of Marimastat (a MMP inhibitor), MMP-2-specific siRNA, MMP-2 defect, and NSMase-specific siRNA. Moreover, upon uPA stimulation, uPAR, MT1-MMP, MMP-2 and NSMase-2 interacted with integrin alpha(v)beta(3), evidenced by co-immunoprecipitation and immunocytochemistry experiments. Moreover, the alpha(v)beta(3) blocking antibody inhibited the uPA-triggered MMPs/uPAR/integrin alpha(v)beta(3) interaction, NSMase-2 activation, Ki67 expression and DNA synthesis in ECV304. In conclusion, uPA triggers interaction between integrin alpha(v)beta(3), uPAR and MMPs that leads to NSMase-2 and ERK1/2 activation and cell proliferation. These findings highlight a new signaling mechanism for uPA, and suggest that, upon uPA stimulation, uPAR, MMPs, integrin alpha(v)beta(3) and NSMase-2 form a signaling complex that take part in mitogenic signaling in ECV304 cells