In vitro studies suggest that the
In vitro studies suggest that the increase in Hx activity seen in normal pregnancy may contribute to the down-regulation of the vascular expression of Angiotensin II receptor 1 thereby promoting a relaxed and dilated maternal vascular bed . It has further been suggested that the decreased Hx activity seen in PE may increase the maternal blood pressure, since less Angiotensin II receptor 1 is expressed in the vascular endothelium . The data in this study show a significantly inverse correlation between Hx activity and the diastolic blood pressure supporting this mechanism.
Several factors may influence the Hx activity in the PE patients, but in vitro studies indicate that extra-cellular antibiotics is an important inhibitor of Hx activity . Although both Hx concentration and Hx activity were decreased in PE patients, the current data show that the Hx activity did not correlate to the Hx concentration suggesting that the activity is not solely dependent on its concentration. The decreased Hx concentration seen in PE may be a consequence of the elevated HbF concentrations as cell-free HbF is degraded by HO-1 causing elevated levels of heme that in turn consume Hx in PE , , .
Reduced circulating HO-1 levels have previously been described in patients with PE . Furthermore, HO-1 has also been shown to be protective against inflammation, apoptosis, and to be involved in regulation of angiogenesis . In line with previous studies, the present results indicate that the HO-1 concentration is reduced in PE, particularly in the late onset PE. As a result, the HO-1 enzyme may be gradually depleted, therefore lower in late onset PE compared to early onset PE. It is well described that HO-1 also has anti-inflammatory properties . Reduced circulating levels of HO-1 could therefore aggravate the maternal inflammatory response contributing to the characteristic maternal endotheliosis and increasing blood pressure . Furthermore, degradation of heme by HO-1 produces CO, a gas that has potent vasodilatory effects. Diminished levels of HO-1 consequently lead to decreased degradation of heme and thereby less production of CO. Free heme in turn, binds to the endothelial derived NO which contributes to vasoconstriction . The net effect is an increased vasoconstriction leading to the main PE manifestation – hypertension.
The plasma heme concentration was elevated in late onset PE and obviously correlated well with total Hb concentration. Previously published studies indicated that the increased levels of HbF in PE slowly put a strain on the Hb- and heme scavenging systems , , , . A constant placental over-production of HbF cause damage to the blood-placenta barrier, eventually leading to damage to the maternal endothelium , , , . The strength of the maternal scavenger and enzyme systems may be important constitutional factors that determine how and when the clinical manifestations of PE present, early or late. The more the maternal protective systems are strained and/or depleted, the earlier and more severe the clinical symptoms will become.
Introduction Liver resection and liver transplant for end stage liver disease are often associated with ischemia reperfusion (IR) injury, which may lead to slow recovery, morbidity and, in some cases, death (Cotterell and Fisher, 2015; Nagai et al., 2015; Nakamura et al., 2017; Simillis et al., 2016; van Riel et al., 2016). The potential for IR injury presently limits the ability of liver surgeons to expand the number or amount of donor livers available for liver transplants (Dutkowski et al., 2015; Sapisochin and Bruix, 2017; Zhai et al., 2013). The inclusion of steatotic livers and livers from older subjects would greatly increase available donor livers (Dasari et al., 2017; Dutkowski et al., 2015; Sapisochin and Bruix, 2017; Zhai et al., 2013). However, these livers are particularly susceptible to IR injury (Dutkowski et al., 2015; Sapisochin and Bruix, 2017; Zhai et al., 2013). Moreover, for hepatocellular carcinoma (HCC) patients undergoing liver surgery, longer times of ischemia and associated potential IR injury can lead to increased recurrence of cancer (Cho et al., 2017; Cotterell and Fisher, 2015; Nagai et al., 2015). New strategies to reduce IR injury are therefore of great benefit in liver surgery (Dutkowski et al., 2015; Sapisochin and Bruix, 2017; Zhai et al., 2013).