bioRxiv Science⌕ Search

Biology subjects

Resseguier, N.

Publications and source records attributed to Resseguier, N..

2 recordsLinked to original sources

Dual specificity phosphate 1 (DUSP1) as a non-invasive circulating biomarker candidate in preeclampsia

BackgroundPreeclampsia (PE) is a multisystem pregnancy complication constituting a major cause of maternal and fetal morbidity and mortality. Factors pointing to a placental origin are the development of the pathology only during pregnancy, and its disappearance in the post-partum period. MethodsHere, we aim to identify new early predictive biomarkers based on a transcriptional signature of PE using RNAseq. Whole blood and serum samples were collected at the time of the first event of PE (V1) and same samples after remote delivery (30-60 postpartum days, V2). These two samples enabled investigation of PE markers found in V1 but absent in V2. To confirm that these candidates are associated with PE, an investigation of associated placental biopsy was also realized (J0). ResultsOur study identified a specific signature of PE including five Gene Ontology clusters including "angiogenesis and differentiation", "cell cycle", "cell adhesion", "inflammatory response" and "cellular metabolism". Interestingly, DUSP1 gene was found specifically modulated in PE. Pregnant women with PE have a higher concentration of DUSP1 in serum compared to healthy donors. Interesting, at a distance from childbirth (V2), DUSP1 finds a rate like the control group showing the predictive interest of DUSP1 as a promising predictive biomarker of PE. ConclusionsThe investigation of DUSP1 in a prospective study with a larger cohort, including the severity aspect of the disease, is necessary to confirm its value as a predictive biomarker in PE.

pathology↗

Clinical and Genetic insights in a tertiary care center cohort of patients with bicuspid aortic valve

BACKGROUNDto describe spectrum of valve function in bicuspid aortic valve (BAV) patients referred to a tertiary care center and to investigate genetic pathways associated with valve degeneration. METHODSAll consecutive patients with BAV were prospectively included from 2014 to 2018. BAV was defined according to embryologic and Sievers classifications. Clinical and echo variables were compared according to aortic valve function. Aortic valve tissues were collected from BAV patients (n=15) operated for severe aortic stenosis (AS-BAV, n=7) or aortic regurgitation (AR-BAV, n=8). RT-qPCR was performed to compare gene expression level in AS-BAV, AR-BAV and controls corresponding to healthy tricuspid aortic valves collected on human heart explant immediately after transplantation (n=5). RESULTSOut of 223 adults with BAV, mean age 53{+/-}17 years, 83% had left-right coronary cusps fusion, 80% Sievers type 1 BAV and 49% aortopathy. Twenty-four patients had normal valve function, 66 patients had AS-BAV, 91 patients had AR-BAV and 40 patient had AR+AS BAV. BAV phenotype did not predict neither AS-BAV nor AR-BAV (all p>0.1). By multivariable analysis, age >50 (41.6[10.3-248.2],p<0.001) and presence of raphe(12.8[2.4-87.4],p<0.001) were significantly associated with AS-BAV and male gender of AR-BAV(5[1.6-16.4], p=0.005). RT-qPCR revealed overexpression of RUNX2 in AS-BAV (17.67{+/-}1.83 vs 3.25{+/-}0.93, p=0.04), and overexpression of COL1A1 (4.01{+/-}0.6vs2.25{+/-}0.5,p=0.03) and FLNA (23.31{+/-}7.5vs1.97{+/-}0.3,p=0.03) in AR-BAV. CONCLUSIONSThis prospective study confirmed high prevalence of valve dysfunction at first diagnosis of BAV in a referred population. Clinical and echo variables are poorly associated with BAV dysfunction. The leaking or stenotic processes could be both supported by dysregulation of specific genetic pathways

genetics↗