• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
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  • 2020-10
  • 2020-11
  • Also our data from this study indicate


    Also, our data from this study indicate that gestational GC exposure altered hematological and hemorheological parameters, however reports exist that altered blood rheological markers are associated with atherosclerosis and CVD (Tzoulaki et al., 2007). Also, the platelet to lymphocyte ratio (PLR) has been recently reported to be a reliable marker of inflammation and resulting atherothrombotic CVD events (Koseoglu et al., 2015). Hence, the findings in this present study that gestational GC exposure caused altered hematological markers that are associated with increased blood viscosity. Interestingly, in the current study is that gestational GC exposure led to increased endoglin that is associated with impaired glucose homeostasis. The finding of La Sala and coworkers that hyperglycemia upregulates endoglin Zerumbone and release in diabetes (La Sala et al., 2015), further corroborate the report of the current study and suggest a connection between endoglin and glucose homeostasis. Although, endoglin is required for normal angiogenesis during foetal development as endoglin null embryos die at 10–11.5 days due to vascular and cardiac abnormalities (Arthur et al., 2000; Li et al., 2003). Several studies have reported elevated endoglin in numerous vascular pathological events, including active site of inflamed tissues, atherosclerosis, in response to arterial injury (Sánchez-Elsner et al., 2002), in wound healing (Torsney et al., 2002), preeclampsia, systemic sclerosis or tumor angiogenesis (Ten Dijke et al., 2008; Wipff et al., 2008) and endometriosis (Fujishita et al., 1999). Several published studies have reported that endoglin negatively regulates TGF-β-mediated signalling in quiescent endothelium (Lebrin et al., 2004) and is involved in endothelial proliferation in response to an injury (Lopez-Novoa and Bernabeu, 2010) and in the inflammation (Rossi et al., 2013). Furthermore, increased plasma levels of endoglin have been associated with diabetic complications (Valbuena-Diez et al., 2012). The involvement of soluble endoglin in a number of widespread pathologies demonstrates that endoglin is not only marker of endothelial integrity but also a causative factor for endothelial dysfunction. Investigators have also suggested that soluble endoglin levels may be used to assess the progression and treatment efficacy of cardiovascular diseases related to endothelial dysfunction (Rathouska et al., 2015). In consonance with our finding that gestational GC exposure led to increase atherogenic dyslipidemia and impaired nitric oxide biosynthesis that is associated with increase endoglin, report exist that endoglin levels increase during the early stages of atherosclerosis due to damaged endothelial cells and then decrease during the later stages of the atherosclerotic process (Li et al., 2000). In another study, the endoglin levels of patients with hypertension and/or type 2 diabetes as well as target-organ damage such as retinopathy, were significantly higher than in the controls (Blázquez-Medela et al., 2010). In addition, endoglin was shown to act synergistically with soluble Flt-1 (sFlt-1), the natural antagonist of vascular endothelial growth factor (VEGF), to induce maternal endothelial dysfunction and severe preeclampsia in animal studies (Venkatesha et al., 2006). Therefore, the observed gestational GC-induced systemic and hepatic inflammation and oxidative stress together with alteration in foetal outcome (decreased foetal and placenta weights) may be due in part to the elevated endoglin in gestational GC-exposed rats. Earlier studies have reported contrasting findings on the effect of GC exposure on DPP-4 activity such as diminished DPP-4 activity on cultured human dermal fibroblasts (Sorrell et al., 2003), increased DPP-4 activity in thymocyte of male rats (Kraml et al., 2003) and unaltered circulating DPP-4 activity in asthmatic patients (Van Der Velden et al., 1999). However, it is interesting to note that the diabetogenic effect of GC exposure during late pregnancy was accompanied by elevated DPP-4 activity in this study. The report of Quarta and coworkers support the involvement of DPP-4 in GC-induced gluco-metabolic dysfunction because mice treated with glucagon-like peptide-1 (GLP-1) had improved glucose homeostasis while GC-exposed mice had impaired glucose homeostasis (Quarta et al., 2017).