Maternal over-nutrition may predispose offspring to obesity, type 2 diabetes and other adult diseases. The present study investigated long-term impact of prenatal high sucrose (HS) diets on cognitive capabilities in aged rat offspring. The fasting plasma glucose concentration did not differ between the control and HS groups. However, the fasting plasma insulin and insulin resistance index values were significantly increased in HS offspring that showed abnormal glucose tolerance test. HS offspring exhibited increased escape latency and swimming path length to the platform, and reduced time in the target quadrant and the number of crossing the platform, as compared with the control group. The expression of Grin2b/NR2B, Wnt2, Wnt3a and active form of β-catenin protein were decreased, and Dickkopf-related protein 1 was increased in the HS group. In addition, the levels of lipid peroxidation biomarker thiobarbituricacid reactive substance, nicotinamide adenine dinucleotide phosphate oxidases 2 and superoxide dismutase 1 were significantly increased, and the activity of catalase was decreased in the hippocampus in the HS group. The results demonstrate that prenatal HS-induced metabolic changes cause cognitive deficits in aged rat offspring, probably due to altered N-methyl-D-aspartate receptors/Wnt signaling and oxidative stress in the hippocampus.
INTRODUCTIONHuman cardiovascular diseases continue to cause major health and economic burden worldwide [1,2]. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs), including both embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), provide an enormous potential for the development of tissue engineering, drug screening, and cardiac disease www.aging-us.com
Placental vascular dysfunction was suggested to be critical for placental ischemia-initiated hypertension in preeclampsia, although the contributions of endothelium involved are unclear. The present study found, unlike non-placental vessels, acetylcholine showed no vasodilatation effect on placental vessels, indicating that endothelial-derived nitric oxide (NO) was extremely weak in placental vessels. Placental vascular responses to exogenous NO from sodium nitroprusside (SNP) were significantly different from non-placental vessels. These results were further confirmed in sheep, and rat vessels. In preeclamptic placental vessels, acetylcholine also showed no vasodilatation effects, while vascular responses to SNP were suppressed, associated with impaired cGMP/sGC pathway in vascular smooth muscle cells (VSMCs). The current theory on placental ischemia-initiated hypertension in preeclampsia focused on changes in placental vascular functions, including endothelial dysfunction. This study found the placental endothelium contributed very poorly to vasodilatation, and altered vascular functions in preeclampsia mainly occurred in VSMCs instead of endothelial cells. The findings contribute importantly to understanding the special feature of placental vascular functions and its pathophysiological changes in the development of hypertension in preeclampsia.
Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway.
BackgroundOne of the most terrible famines last century was Great Chinese Famine (GCF) in 1959~1961 when millions of people died from starving. Under-nutrition during famine between the Western and Eastern (Dutch Hungry vs. GCF) was similar, while cardiovascular consequences might not be the same. Addressing such questions may gain new insight into prevention of cardiovascular diseases.MethodsA retrospective cohort of 18,593 participants aged 43–49 years of old, was from Suzhou, China. Logistic regression model was used to calculate the relative risk (RR) of hypertension and corresponding 95% confidence interval (CI). The multivariate RRs were adjusted for age, plasma glucose, triglyceride, and cholesterol.ResultsThe multivariate RRs of systolic and diastolic pressure were not significantly elevated in the rural subgroups, but was higher in the urban population born in the famine (systolic pressure adjust RR 1.382, 95% CI 1.235–1.545, diastolic pressure adjust RR 1.569, 95% CI 1.415–1.740). The risks of hypertension were significantly higher among the urban subjects than that in the rural subgroups (systolic hypertension adjust RR 2.915, 95% CI 2.616–3.249, diastolic hypertension adjust RR 4.568, 95% CI 4.079–5.116). Percentile of optimal diastolic pressure at mid-age was significantly lower in the urban population prenatally exposed to the famine regardless of sexes. However, a similar reduction of percentage of optimal systolic pressure was only seen in the female, not the male population in the urban region.ConclusionThe data suggest Asian genetic basis was not able to block famine-programmed vascular diseases as that happened in Europe, and the programmed problems due to under-nutrition could be reversed after birth. Protective mechanisms may be related to diet habits before age of 30 years old, which is important contribution to early prevention of hypertension.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.