While initial studies suggested that Nox2−/− mice were not protected from pressure overload-induced cardiac hypertrophy [75,76], more recent studies have reported protection from pressure overload-induced cardiac hypertrophy and fibrosis and improved cardiac hemodynamics compared to wildtype mice, which was associated with reduced activation of ERK1/2, p38, and JNK MAPK signaling cascades [77]. This evidence concerns the gene MAPK3 and cardiac hypertrophy.