Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance

Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity. Piezo1 is responsible for flow-sensitive non-inactivating non-selective cationic channels which depolarize the membrane potential. As fluid flow increases, depolarization increases to activate voltage-gated Ca2+ channels in the adjacent vascular smooth muscle cells, causing vasoconstriction. Physical performance is compromised in mice which lack endothelial Piezo1 and there is weight loss after sustained activity. The data suggest that Piezo1 channels sense physical activity to advantageously reset vascular control

Post-partum follow-up of women with gestational diabetes mellitus: Effectiveness, determinants, and barriers

Background: Despite the recommendations for postpartum blood glucose monitoring post gestational diabetes mellitus (GDM); scientific evidence reveals that these recommendations may not be fully complied to. This study aimed to follow-up women up to 2 years post-delivery with pregnancies complicated by GDM and healthy controls to assess this fact.Methods: Women with GDM (n = 78) and normal glucose tolerant (n = 89) delivered in 2014 were followed up for 2 years. They were informed and enquired via telephone about their blood glucose screening, physical activity, postpartum complications, and current weight status of mother and baby.Results: Women with previous GDM were older and reported higher body weight 2 years post-delivery. At the 2 year follow-up, n = 11 (14.1%) participants had developed diabetes, all with previous GDM. Both weight at birth (3.8 ± 0.5 kg) and at 2-year (10.7 ± 2.3 kg) for the babies born to GDM mothers was significantly higher than the NGT group babies (2.6 ± 0.63 and 7.1 ± 1.4 kg; p \u3c .05). Only 27 women regularly opted for T2DM screening via monitoring blood glucose or HbA1c levels postpartum. The top reason for failed screening included: believing that GDM would disappear after delivery, and being occupied with the baby.Conclusions: The high incidence of T2DM in women with previous GDM is an alarming finding. Given this trend, systematic follow-up programs are needed to reduce obesity and diabetes risk

Vascular Endothelial Growth Factor Receptor-2 Couples Cyclo-Oxygenase-2 with Pro-Angiogenic Actions of Leptin on Human Endothelial Cells

The adipocyte-derived hormone leptin influences the behaviour of a wide range of cell types and is now recognised as a pro-angiogenic and pro-inflammatory factor. In the vasculature, these effects are mediated in part through its direct leptin receptor (ObRb)-driven actions on endothelial cells (ECs) but the mechanisms responsible for these activities have not been established. In this study we sought to more fully define the molecular links between inflammatory and angiogenic responses of leptin-stimulated human ECs../Akt/COX-2 signalling axis is required for leptin's pro-angiogenic actions and that this is regulated upstream by ObRb-dependent activation of VEGFR2. These studies identify a new function for VEGFR2 as a mediator of leptin-stimulated COX-2 expression and angiogenesis and have implications for understanding leptin's regulation of the vasculature in both non-obese and obese individuals