Abstract Peripheral artery disease (PAD) affects 8.5 million of Americans over 40 years of age. mircroRNAs (miRs) are endogenous 21∼25 nucleotides noncoding RNA, that can regulate posttranscriptional gene expression. The most common mechanism of action of miRs is by binding to the 3' un-translated region of a target mRNA and thereby reducing mRNA expression or protein translation. Circulating miRNAs, represent potential biomarkers for the diagnosis and prognosis of PAD and a start point for individualized treatment. Recent evidence from our first R01 suggests that mircroRNA-210 (miR-210) expression in the skeletal muscle of PAD patients (intermittent claudication and critical limb ischemia) is an important biomarker that targets the iron-sulfur cluster scaffold homolog and cytochrome c oxidase assembly protein genes leading to decreased mitochondrial respiration. In this R01 renewal we want to go a step further and investigate all the targets of miR-210 using an omics approach. We are bringing together an excellent team of vascular surgeons, biomedical researchers and omics experts to investigate how miR-210 and its downstream targets affect the skeletal muscle and the vasculature of PAD and non-PAD controls. To that end, Aim #1, will identify downstream targets of miR-210 using an omics approach in PAD and non-PAD controls. Aim #2, will determine the effect of revascularization operations in decreasing miR- 210 expression and associate these changes with walking function and quality of life parameters. Aim#3, will determine health disparities in Hispanic origin PAD patients. Addressing these aims, will provide for the first time, a complete analysis of all the changes in skeletal muscle and vasculature of PAD patients that undergoing a revascularization operation using the omics approach.