Nutrition Interventions for Lowering Cardiovascular Risk After Hypertensive Disorders of Pregnancy: A Systematic Review.

Background: Hypertension is one of the most common medical problems during pregnancy. Hypertensive disorders of pregnancy (HDP) increase the risk of premature cardiovascular disease (CVD) 2- to 4-fold within 10 years after delivery. Early health behaviour modifications may prevent or manage several cardiovascular risk factors. Importantly, compared with women without HDP, fewer women with HDP achieve national dietary guidelines to prevent CVD. This highlights an opportunity for programs tailored for women post-HDP to support their nutritional behaviours as a key component of postpartum CVD preventive care. This systematic review investigated the impacts of nutrition modifications on lowering measures of CVD risk after HDP. Methods: Four electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Library) were searched in October 2022 with a search strategy focused on nutrition programs/interventions and women post-HDP. Additional inclusion criteria were original research and reported outcome of CVD risk or cardiovascular risk factors. Results: Six studies were included: 4 experimental trials and 2 prospective cohort studies. Of the nutrition interventions, 4 were embedded within comprehensive health behaviour intervention programs. Outcome measures varied, but all studies reported blood pressure. A narrative synthesis found that the range of changes in blood pressure varied from no change to clinically meaningful change. Conclusions: This review found statistically nonsignificant yet clinically important improvements in measures of cardiovascular risk across a range of nutritional interventions in women after HDP. Further high-quality evidence is needed to inform the design and implementation of nutritional preventive cardiovascular care targeting this high CVD-risk population.

Contexte: L'hypertension est l'un des problèmes médicaux les plus fréquents durant la grossesse. Les troubles hypertensifs de la grossesse (THG) font augmenter le risque de maladies cardiovasculaires (MCV) prématurées de 2 à 4 fois dans les 10 années après l'accouchement. Des modifications précoces des comportements liés à la santé peuvent permettre de prévenir ou de prendre en charge plusieurs facteurs de risque cardiovasculaire. Notamment, par rapport aux femmes sans THG, moins de femmes atteintes de THG se conforment aux lignes directrices nationales en matière d'alimentation pour prévenir les MCV. D'où la possibilité qui s'offre aux programmes adaptés aux femmes post-THG d'encourager l'adoption de leurs comportements nutritionnels, une composante essentielle des soins de prévention des MCV dans la période du post-partum. La présente revue systématique visait à examiner les répercussions des modifications nutritionnelles sur la réduction des mesures du risque de MCV après les THG. Méthodes: En octobre 2022, nous avons effectué des recherches dans 4 bases de données électroniques (MEDLINE, Embase, CINAHL, Cochrane Library) au moyen d'une stratégie de recherche axée sur les interventions/programmes nutritionnels et les femmes post-THG. Les critères d'inclusion supplémentaires étaient la recherche initiale et les résultats signalés du risque de MCV ou des facteurs de risque cardiovasculaire. Résultats: Nous avons tenu compte de 6 études : 4 essais expérimentaux et 2 études de cohorte prospectives. Parmi les interventions nutritionnelles, 4 étaient intégrées aux programmes exhaustifs d'interventions sur les comportements liés à la santé. Les critères de jugement variaient, mais la pression artérielle était signalée dans toutes les études. Une synthèse narrative a permis de constater que l'étendue des changements dans la pression artérielle allait d'une absence de changement à des changements significatifs sur le plan clinique. Conclusions: Cette revue a permis de constater des améliorations non significatives sur le plan statistique, mais importantes sur le plan clinique des mesures du risque cardiovasculaire de différentes interventions nutritionnelles chez les femmes après les THG. D'autres données probantes de grande qualité sont nécessaires pour faciliter l'élaboration et la mise en œuvre de soins de prévention nutritionnelle des maladies cardiovasculaires visant cette population exposée à un risque élevé de MCV.

GEF-H1 Transduces FcεRI Signaling in Mast Cells to Activate RhoA and Focal Adhesion Formation during Exocytosis.

When antigen-stimulated, mast cells release preformed inflammatory mediators stored in cytoplasmic granules. This occurs via a robust exocytosis mechanism termed degranulation. Our previous studies revealed that RhoA and Rac1 are activated during mast cell antigen stimulation and are required for mediator release. Here, we show that the RhoGEF, GEF-H1, acts as a signal transducer of antigen stimulation to activate RhoA and promote mast cell spreading via focal adhesion (FA) formation. Cell spreading, granule movement, and exocytosis were all reduced in antigen-stimulated mast cells when GEF-H1 was depleted by RNA interference. GEF-H1-depleted cells also showed a significant reduction in RhoA activation, resulting in reduced stress fiber formation without altering lamellipodia formation. Ectopic expression of a constitutively active RhoA mutant restored normal morphology in GEF-H1-depleted cells. FA formation during antigen stimulation required GEF-H1, suggesting it is a downstream target of the GEF-H1-RhoA signaling axis. GEF-H1 was activated by phosphorylation in conjunction with antigen stimulation. Syk kinase is linked to the FcεRI signaling pathway and the Syk inhibitor, GS-9973, blocked GEF-H1 activation and also suppressed cell spreading, granule movement, and exocytosis. We concluded that during FcεRI receptor stimulation, GEF-H1 transmits signals to RhoA activation and FA formation to facilitate the exocytosis mechanism.

Fgd5 is a Rac1-specific Rho GEF that is selectively inhibited by aurintricarboxylic acid.

Rho proteins are signalling molecules that control cellular dynamics, movement and morphological changes. They are activated by Rho guanine-nucleotide exchange factors (Rho GEFs) that transduce upstream signals into Rho-mediated activation of downstream processes. Fgd5 is a Rho GEF involved in angiogenesis and its target Rho protein for this process has been linked to Cdc42 activation. Here, we examined the function of purified Fgd5, specifically, which Rho proteins it activates and pinpoint the structural domains required for enzymatic activity. Using a GEF enzyme assay, we found that purified Fgd5 showed preferential activation of Rac1 and direct binding of Rac1 in pull-down and co-immunoprecipitation assays. Structural comparisons showed that the Fgd5 DH domain is highly similar to the Rac1 GEF, TrioN, supporting a role for Fgd5 as a Rac1 GEF. Compounds that bind to purified Fgd5 DH-PH protein were identified by screening a small molecule library via surface plasmon resonance. The effects of eleven ligands were further examined for their ability to inhibit the Fgd5 GEF enzymatic activity and Rac1 interaction. From these studies, we found that the compound aurintricarboxylic acid, and to a lesser extent mitoxantrone dihydrochloride, inhibited both Fgd5 GEF activation of Rac1 and their interaction. Aurintricarboxylic acid had no effect on the activity or binding of the Rac1 GEF, TrioN, thus demonstrating the feasibility of selectively disrupting Rho GEF activators. Abbreviations: a.a.: amino acid; ATA: aurintricarboxylic acid; DH: Dbl homology; DOCK: dictator of cytokinesis; Fgd: faciogenital dysplasia; GEF: guanine-nucleotide exchange factor; GST: glutathione S-transferase; LOPAC: library of pharmacologically active compounds; PH: pleckstrin homology; PDB: protein data bank; s.e.m.: standard error of the mean; SPR: surface plasmon resonance.