Embodiments of the present disclosure relate generally to the treatment and prevention of ischemic injury. More particularly, embodiments of the present disclosure include materials and methods for treating and preventing ischemic injury caused by diseases like peripheral artery disease (PAD) by modulating various candidate genes within the Lsq-1 QTL, such as Bcl-2-associated athanogene-3 (Bag3). Given that no alleles that modulate a subject's susceptibility to conditions like critical limb ischemia are presently known, there is a need to identify the genetic determinants that play important roles in the treatment and prevention of ischemic injury.