[Evaluation of a woman's care program after pre-eclampsia]. / Évaluation d'un parcours de soin chez la femme au décours d'une prééclampsie.

INTRODUCTION: The medical treatment of preeclampsia is well structured in its acute phase but the required follow-up with patients in post-partum is discussed. However, preeclampsia is associated with an increased risk of cardiovascular morbi-mortality in the long term. In order to optimize the post-partum treatment, a care program has been developed for these patients in the city of Nantes, France. This includes a check-up of the cardiovascular risks at a day hospital. Our study presents the first results of this program. METHODS: The study included 134 patients who were diagnosed with preeclampsia between October 2016 and January 2019 in the Nantes area, France, and took part in the program within the year following their childbirth. A descriptive analysis was first carried out and then a multivariate logistic regression model was used to investigate the risk factors for persistent high blood pressure after preeclampsia. RESULTS: The study detected 28 cases of persistent hypertension (20.9%), 34 cases of obesity (25.3%) and 1 case of diabetes. Hypertension was predominantly diastolic, mild and sometimes masked (35.7%). In a third of the cases (32.1%), the hypertension was secondary. High blood pressure was found to be more frequent in older patients (OR: 2.26; 95% CI: 1.25-4.11, p=0.072), patients from sub-Saharan Africa (OR: 11.52; 95% CI: 2.67-49.86, p=0.01) and multiparous patients (OR: 7.82; 95% CI: 1.15-53.21, p=0.035). CONCLUSION: The study confirmed that this care program enables an earlier detection and therefore treatment of the cardiovascular risk factors of these young women.

Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial.

BACKGROUND: The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy. METHODS AND RESULTS: The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of ≤35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5×10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA-guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4±2.0% versus 35.7±2.5%; p=0.003), LV end-systolic volume (167.8±18.8mL versus 156.1±28.6mL; p=0.04), 6-min walk test and NYHA functional class. CONCLUSIONS: Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT01076920.

Large-scale mRNA analysis of female skeletal muscles during 60 days of bed rest with and without exercise or dietary protein supplementation as countermeasures.

Microgravity has a dramatic impact on human physiology, illustrated in particular, with skeletal muscle impairment. A thorough understanding of the mechanisms leading to loss of muscle mass and structural disorders is necessary for defining efficient clinical and spaceflight countermeasures. We investigated the effects of long-term bed rest on the transcriptome of soleus (SOL) and vastus lateralis (VL) muscles in healthy women (BRC group, n = 8), and the potential beneficial impact of protein supplementation (BRN group, n = 8) and of a combined resistance and aerobic training (BRE group, n = 8). Gene expression profiles were obtained using a customized microarray containing 6,681 muscles-relevant genes. A two-class statistical analysis was applied on 2,103 genes with consolidated expression in BRC, BRN, and BRE groups. We identified 472 and 207 mRNAs whose expression was modified in SOL and VL from BRC group, respectively. Further clustering analysis, identifying relevant biological mechanisms and pathways, reported five main subclusters. Three are composed of upregulated mRNAs involved mainly in nucleic acid and protein metabolism, and two made up of downregulated transcripts encoding components involved in energy metabolism. Exercise countermeasure demonstrated drastic compensatory effects, decreasing the number of differentially expressed mRNAs by 89 and 96% in SOL and VL, respectively. In contrast, nutrition countermeasure had moderate effects and decreased the number of differentially-expressed transcripts by 40 and 25% in SOL and VL. Together, these data present a systematic, global and comprehensive view of the adaptive response of female muscle to long-term atrophy.

DNA chip technology in cardiovascular research.

Global and/or dynamic analysis of the cardiac transcriptome may improve our understanding of the adaptation of cardiac tissue or cells to different physiological or pathological conditions. The achievement of sequencing projects on mammalian genomes and the development of DNA chip technology have dramatically extended the scale of gene expression studies from a candidate gene approach to a system approach. In current DNA chip experiments, expression levels of thousands of genes can be determined simultaneously. Obviously, the huge quantities of objects and information generated by these experiments require a computational management of the expression data with adequate mathematical (mostly statistical) algorithms. Here, we will discuss the principle and experimental key points of DNA chips. Four examples will be cited to illustrate applications in the cardiovascular system.

Transcriptomal analysis of failing and nonfailing human hearts.

Heart failure is a multifactorial disease that may result from different initiating events. To contribute to an improved comprehension of normal cardiac function and the molecular events leading to heart failure, we performed large-scale gene expression analysis of failing and nonfailing human ventricle. Our aim was to define and compare expression profiles of 4 specific pathophysiological cardiac situations: 1) left ventricle (LV) from nonfailing heart; 2) LV from failing hearts affected by dilated cardiomyopathy (DCM); 3) LV from failing hearts affected by ischemic CM (ICM); 4) right ventricle (RV) from failing hearts affected by DCM or ICM. We used oligonucleotide arrays representing approximately 12,000 human genes. After stringent numerical analyses using several statistical tests, we identified 1,306 genes with a similar expression profile in all 4 cardiac situations, therefore representative of part of the human cardiac expression profile. A total of 95 genes displayed differential expression between failing and nonfailing heart samples, reflecting a reversal to developmental gene expression, dedifferentiation of failing cardiomyocytes, and involvement of apoptosis. Twenty genes were differentially expressed between failing LV and failing RV, identifying possible candidates for different functioning of both ventricles. Finally, no genes were found to be significantly differentially expressed between failing DCM and failing ICM LV, emphasizing that transcriptomal analysis of explanted hearts results mainly in identification of expression profiles of end-stage heart failure and less in determination of expression profiles of the underlying etiology. Taken together, our data resulted in identification of putative transcriptomal landmarks for normal and disturbed cardiac function.