Search

Abstract: Estrogen has a protective effect on the cardiovascular system. Yet the mechanism of how estrogen inhibits vascular smooth muscle cell (VSMC) proliferation after vascular injury and the role of caveolin-1 in this process are not clear. To understand the protection effect of estrogen and caveolin-1, we employed a vascular balloon-injury model. Sixteen New Zealand White rabbits with or without estrogen were tested. 17β-estradiol is able to inhibit VSMC proliferation in a range from 10−10–10−5 mol/L, with an optimal concentration of 10−8 mol/L. Estrogen exerted its effect through suppressing the activity of p42/44 MAPK, which can be blocked by tamoxifen. Moreover, in estrogen pretreated cells as well as in common carotid arteries of the balloon injury model, expression of caveolin-1 is enhanced compared to the estrogen-deficient group, as assessed by both western blotting and RT-PCR and morphological studies. Our results showed that the inhibition effect of estrogen in VSMCs is mediated by p42/44 MAPK. Caveolin-1 plays an important role in this protective process. [Copyright &y& Elsevier]

Abstract: Objective: Intrauterine growth restriction (IUGR) is associated with hypertension and chronic kidney disease in adulthood. Postnatal overnutrition after IUGR may be of pathogenic importance for the development of diabetes and cardiovascular disease. This study was to identify the effects of IUGR and a postnatal high-protein diet on the kidneys in adult rats. Methods: Intrauterine growth restriction was induced in Sprague-Dawley rats by isocaloric protein restriction in pregnant dams. IUGR pups were divided into two groups that were a standard-protein diet (IUGR group) or a high-protein diet (HP group). A comparative proteomic method was used to study the differences of protein expression profiles between normal adult rats and adult rats with IUGR and the effects of a postnatal high-protein diet on the protein expression profiles of the kidneys. Results: The IUGR adults had higher urinary excretion of protein and blood pressure than controls and the HP diet caused more severe hypertension and proteinuria than IUGR itself. The differential proteomic expression analysis found 12 proteins that had significantly differential expression between the IUGR and control groups, which were transcription regulators and structural molecules. The differential proteomic expression analysis between the HP and control groups found 13 proteins that had significantly differential expression and were involved primarily in body metabolism, oxidation reduction, and apoptosis regulation. Conclusion: An HP diet intervention after IUGR worsens the severity of hypertension and proteinuria, and this study may provide valuable experimental evidence of proteins involved in the pathogenesis of kidney disease in IUGR and the effect of postnatal overnutrition. [Copyright &y& Elsevier]

• Icariin was also found to protect against diet-induced obesity and insulin resistance. • Irisin, a recently identified myokine, regulates energy metabolism by inducing browning of white adipose tissue. • Icariin in vitro increased irisin/FNDC5 in C2C12 myotubes via AMPK pathway. • Icariin invivo decreased body weight in C57BL/6 mice and increased FNDC5 and p-AMPK expression in skeletal muscle. Backgroud Icariin, a major bioactive pharmaceutical component of the Chinese herbal medicine Epimedii Herba, has demonstrated lipid-lowering and anti-obesity effects. Irisin/ fibronectin type III domain-containing 5 (FNDC5) protects against obesity by inducing browning in white adipose tissue. Objectives This study investigated the effects of icariin on irisin/FNDC5 expression in C2C12 myotubes. Method Cultured murine C2C12 myocytes were used to study the effects of icariin on irisin/FNDC5 expressions by Western-blot, qPCR, Elisa and Immunofluorescence. We also investigated FNDC5 expression in icariin-treated intact mice. Results Icariin increased irisin/FNDC5 protein levels. mRNA levels of irisin/FNDC5 were also increased in C2C12 myocytes after treatment with icariin. Icariin increased peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α) protein and mRNA levels. Additionally, icariin exposure resulted in phosphorylation of AMP-activated protein kinase (AMPK) in a dose-dependent manner. The regulatory effect of icariin on FNDC5 protein expression was blocked by the AMPK antagonist compound C or silencing of AMPK, suggesting that icariin increased FNDC5 protein expression via the AMPK pathway. In vivo, icariin decreased body weight gain in C57BL/6 mice and increased FNDC5, PGC-1α, and p-AMPK expression levels in skeletal muscle. Conclusions Taken together, our results indicated that icariin induces irisin/FNDC5 expression via the AMPK pathway, indicating that icariin may be promising as an anti-obesity drug. [ABSTRACT FROM AUTHOR]