NOS3 and endothelial dysfunction: In ACLD, intrahepatic endothelial dysfunction is multifactorial, and involves defective NO production due to decreased endothelial nitric oxide synthase (eNOS) activity, insufficient Krüppel-like factor 2 (KLF-2) expression, Rho A–Rho kinase dysregulation, increased asymmetric dimethylarginine (ADMA) production and, very importantly, NO scavenging by free oxygen radicals due to excessive oxidative stress [17].