Altered Mitochondrial Opa1-Related Fusion in Mouse Promotes Endothelial Cell Dysfunction and Atherosclerosis.

Flow (shear stress)-mediated dilation (FMD) of resistance arteries is a rapid endothelial response involved in tissue perfusion. FMD is reduced early in cardiovascular diseases, generating a major risk factor for atherosclerosis. As alteration of mitochondrial fusion reduces endothelial cells' (ECs) sprouting and angiogenesis, we investigated its role in ECs responses to flow. Opa1 silencing reduced ECs (HUVECs) migration and flow-mediated elongation. In isolated perfused resistance arteries, FMD was reduced in Opa1+/- mice, a model of the human disease due to Opa1 haplo-insufficiency, and in mice with an EC specific Opa1 knock-out (EC-Opa1). Reducing mitochondrial oxidative stress restored FMD in EC-Opa1 mice. In isolated perfused kidneys from EC-Opa1 mice, flow induced a greater pressure, less ATP, and more H2O2 production, compared to control mice. Opa1 expression and mitochondrial length were reduced in ECs submitted in vitro to disturbed flow and in vivo in the atheroprone zone of the mouse aortic cross. Aortic lipid deposition was greater in Ldlr-/--Opa1+/- and in Ldlr-/--EC-Opa1 mice than in control mice fed with a high-fat diet. In conclusion, we found that reduction in mitochondrial fusion in mouse ECs altered the dilator response to shear stress due to excessive superoxide production and induced greater atherosclerosis development.

Assessment of SARS-CoV-2 serological tests for the diagnosis of COVID-19 through the evaluation of three immunoassays: Two automated immunoassays (Euroimmun and Abbott) and one rapid lateral flow immunoassay (NG Biotech).

BACKGROUND: The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose. OBJECTIVES: The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies. METHODS: Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples. RESULTS: Overall sensitivity for IgG was equivalent (around 80 %) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, >14 days after onset of symptoms, was 100.0 % for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98 %) compared to ELISA (95.8 %). Specificity was significantly different between IgA ELISA (78.9 %) and IgM LFIA (95.8 %) (p < 0.05). The best agreement was observed between CLIA and LFIA assays (97 %; k = 0.936). CONCLUSION: Excellent sensitivity for IgG detection was obtained >14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories.

[Multiparametric biochemical analysis revealing an increase of homocysteinemia and NT-proBNP in hypertensive patients living in Bamako (Mali)]. / Analyse biochimique multi-paramétrique révélant une augmentation de l'homocystéinémie et du NT-ProBNP chez les patients hypertendus à Bamako (Mali).

INTRODUCTION: Arterial hypertension is a major public health problem in sub-Saharan Africa due to its high frequency and to the cardiovascular risk that it entails. The purpose of this study was to assess the prevalence of clinical and biological risk factors of hypertension in Bamako (Mali). METHODS: We conducted a case-control study, stratified in function of the sex, of 72 participants including 36 patients with hypertension and 36 controls. Twenty-two plasma biochemical parameters have been measured and analyzed using univariate and multivariate tests. RESULTS: Hyperhomocysteinemia was found in 55.6% of women (p = 0.03) and 100% of men (p = 0.007) with hypertension. High NT-proBNP was also found in 16.7% of women (VIP > 1 in multivariate model) and of men with hypertension (p = 0.00006). A good multivariate predictive model (OPLS-DA) was only obtained in women with high blood pressure, with Q2cum = 0.73, attesting severe sexual dimorphism associated with arterial hypertension. This model involved eight parameters whose plasma concentration was modified (homocysteine, NT-proBNP, potassium, urea, blood glucose, sodium, chlorine and total proteins). CONCLUSION: We registered a significant association between hyperhomocysteinemia and arterial hypertension. Therefore, the assay of homocysteine associated with good management would decrease the risk of cardiovascular diseases while improving the quality of life of hypertensive patients.

Analyse biochimique multi-paramétrique révélant une augmentation de l'homocystéinémie et de la NT-ProBNP chez les patients hypertendus à Bamako (Mali)

Introduction: l'hypertension artérielle est un problème majeur de santé publique en Afrique subsaharienne par sa fréquence élevée et le risque cardiovasculaire qu'elle entraine. L'objectif de cette étude était d'évaluer la prévalence des facteurs de risques cliniques et biologiques de l'hypertension artérielle à Bamako (Mali).Méthodes: il s'agit d'une étude cas-témoin, stratifiée en fonction du sexe, portant sur 72 participants dont 36 hypertendus et 36 contrôles. Vingt-deux paramètres biochimiques plasmatiques ont été mesurés et analysés par des tests univariés et multivariés.Résultats: une hyperhomocystéinémie a été retrouvée chez 55,6% des femmes (p = 0,03) et 100% des hommes (p = 0,007) hypertendus. Le N-terminal pro B-type natriuretic peptide (NT-ProBNP) était également augmenté chez 16,7% des femmes (VIP > 1 dans le modèle multivarié) et des hommes hypertendus (p = 0,00006). Un bon modèle multivarié prédictif (OPLS-DA) a uniquement été obtenu chez les femmes hypertendues, avec un Q2cum = 0,73, attestant ainsi d'un important dimorphisme sexuel associé à l'hypertension artérielle. Ce modèle impliquait huit paramètres dont la concentration plasmatique était modifiée (homocystéine, NT-ProBNP, potassium, urée, glycémie, sodium, chlore et protéines totales).Conclusion: nous avons noté une association significative entre l'hyperhomocystéinémie et l'hypertension artérielle. Par conséquent, le dosage de l'homocystéine associé à une bonne prise en charge diminuerait le risque cardiovasculaire tout en améliorant la qualité de vie des patients hypertendus

Reproducibility of blood tests of liver fibrosis in clinical practice.

OBJECTIVES: To evaluate the inter-laboratory reproducibility of blood test for liver fibrosis: FibroMeter, Fibrotest, APRI and their composites variables. DESIGN AND METHODS: Four studies, including 147 patients, were performed: study #1 included 2 metachronous blood samples and 2 laboratories; studies #2, #3 and #4 included synchronous samples with assays delayed at day 1 in 12 laboratories, at day 0 in 10 laboratories and at day 0 or 1 in 2 laboratories, respectively. Agreement was evaluated by the intraclass correlation coefficient (r(ic)). RESULTS: In studies #1, #2 and #4, r(ic) for FibroMeter was 0.893, 0.942 and 0.991, respectively. In study #3, the r(ic) were: FibroMeter: 0.963, Fibrotest: 0.984, APRI: 0.949. Large simulated variations in composite variables had a weak impact on FibroMeter. CONCLUSIONS: When blood marker limits are controlled, inter-laboratory agreement of blood tests is excellent in clinical practice conditions. Blood tests are robust against the variability of composite blood variables.