No abstract

rhNRG-1 treatment attenuates pulmonary arterial and RV remodelling, and dysfunction in a rat model of MCT-induced PAH and has direct anti-remodelling effects on the pressure-overloaded RV.

SummarySo far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis.

There is increasing evidence that ACE2/angiotensin 1 - 7/Mas receptor axis has a key role in RAS activity regulation with significant pathophysiological implications in several disease states. A therapeutic intervention at this level may open new doors and change the current approach to RAS targeting.

Intrauterine fetal conditions can have lifelong cardiovascular effects. The impact of maternal diabetes mellitus on children’s cardiovascular profile is not well established. The goal of this study was to explore the association between maternal diabetes mellitus and offspring’s blood pressure (BP) ≤10 years of age. Generation XXI is a prospective birth cohort, which enrolled 8301 mother-offspring pairs, including 586 (7.1%) children of diabetic mothers. The associations between maternal diabetes mellitus and BP at 4, 7, and 10 years of age was modeled using linear regression. A mixed-effects model was built to assess differences in BP variation over time. Path analysis was used to quantify effects of potential mediators. Maternal diabetes mellitus was associated with higher BP in offspring at the age of 10 (systolic: β, 1.48; 95% CI, 0.36–2.59; and diastolic: β, 0.86; 95% CI, 0.05–1.71). This association was independent of maternal perinatal characteristics, and it was mediated by child’s body mass index and, to a lesser extent, by gestational age, type of birth, and birth weight (indirect effect proportion, 73%). No significant differences in BP were found at 4 and 7 years of age. Longitudinal analysis showed an accelerated systolic BP increase on maternal diabetes mellitus group (β, 1.16; 95% CI, 0.03–2.28). These finding were especially relevant in males, suggesting sex differences in the mechanisms of BP prenatal programing. Our results provide further evidence that maternal diabetes mellitus is associated with high BP late in childhood, demonstrating a significant role of child’s body mass in the pathway of this association.