RISP-dependent increased mitochondrial ROS and NOX-derived ROS may also lead to DNA damage, ATM activation, Chk1 and Chk2 operating, and enhanced cell cycle progression, as well as inhibited apoptosis, thereby causing increased PASMC proliferation, PA vasoremodeling, and PH in COPD. Here, CHEK2 is linked to chronic obstructive pulmonary disease.