However, more recent
studies have demonstrated that angiogenesis is important for the formation of the new blood vessels. Evidence supporting a role for angiogenesis in the pathogenesis of PH is overexpression of the potent angiogenic factor, vascular endothelial growth factor (VEGF). Although the mechanisms of PH are complex, it can be explained as follows:[2, 6, 7] 1 The hepatic vasodilators: nitric oxide (NO) is a powerful endogenous vasodilator that modulates the intrahepatic vascular tone. In the cirrhotic liver, the synthesis of NO is insufficient to compensate for the activation of vasoconstrictors. Carbon monoxide (CO) is the initial product of heme oxidation by the enzyme, heme oxygenase (HO-1), and is an important modulator of intrahepatic vascular resistance. LDE225 solubility dmso C646 manufacturer Therefore, beside the structural alterations (fibrosis, nodule formation), there is a complex dynamic component that contributes to increasing hepatic vascular resistance
and splanchnic vasodilatation. Understanding this pathophysiology has revealed markers that are associated with the presence of PH and varices. On the other hand, variation of the genes that encode proteins involved in systemic and splanchnic vasodilatation have been found to be associated with the presence of esophageal varices. Therefore, variation of these genes could play a role in addition to predicting the presence of esophageal varices, as well as their likelihood of bleeding. In this issue of the journal, Yang and colleagues have analyzed 951 patients with cirrhosis of various etiologies. The main aim was to evaluate additional blood markers and genetic risk for the prediction of the presence of esophageal varices in cirrhosis. Also, they performed a 2-year follow-up
to evaluate predictors for esophageal varices (EV) bleeding. The authors also studied another 650 independent patients to confirm the association between genetic variants and presence of EVs, namely for validation cohort. The factors analyzed in this study included plasma levels of soluble CD163 (sCD163), VEGF and HO-1, genetic polymorphisms of HO-1, VEGF, and vascular endothelial selleck screening library growth factor receptor 2 (VEGFR2). Soluble CD163 is a specific marker of activated macrophages, another potential biomarker for PH in cirrhosis. The activation of Kupffer cells may be involved in PH by the release of vasoconstrictor substances. Recently, Grønbaek et al. have shown that sCD163 plasma concentration in cirrhosis is almost three times higher than in controls, and sCD163 was an independent predictor of the hepatic venous pressure gradient. Yang et al. found that serum sCD163 level was elevated in patients with cirrhosis complicated by esophageal varices, and this marker could potentially be used to predict the presence of EVs in clinical practice.