Nox4−/− or Nox2−/− mice, EC-specific Nox4, dominant-negative Nox4 or EC-specific catalase-overexpressing mice [35,41,64,65] reveal that Nox2 or Nox4 or their regulators are required for ROS-dependent angiogenic signaling in ECs, tumor angiogenesis as well as post-ischemic neovascularization using a PAD model [8,36,59,62,65,66,67,68,69,70,71,72,73,74,75]. This evidence concerns the gene NOX4 and peripheral arterial disease.