The Impact of Branched-Chain Amino Acid Metabolism on Limb Dysfunction in PAD

Inclusion/exclusion criteria for Healthy Subjects Inclusion criteria * Male or female, age ≥ 50 years old * Non-smoker Exclusion criteria * Presence of peripheral artery disease * History of a heart attack or stroke * Diabetes * Active cancer * Severe renal disease (CrCl \< 60) * Severe liver disease * Active rheumatological diseases Inclusion/exclusion criteria for PAD Subjects Inclusion criteria * Male or female, age 50 years or older * Atherosclerotic PAD, ABI ≤0.85 * Willing to comply with protocol, attend follow-up appointments, complete all study assessments, and provide informed consent * For Aim 3, subjects will have Rutherford stage 4 or 5 disease * For Aim 3, subjects will be undergoing revascularization as standard of care Exclusion criteria * Presence of a femoral, popliteal or tibial aneurysm of the index limb * Life expectancy less than 2 years * A vascular disease prognosis that includes an anticipated above ankle amputation on index limb within 4 weeks of index procedure * Renal dysfunction defined as MDRD eGFR ≤ 20ml/min/173 m2 at the time of screening * Currently on dialysis or history of a renal transplant * Cirrhosis or active hepatitis * A documented hypercoagulable state * Myocardial infarction within 6 months * Stroke within 6 months * Nonatherosclerotic occlusive disease of the lower extremity * Any prior infrainguinal revascularization on index limb * Current immunosuppressive medication, chemotherapy or radiation therapy * Inability to have an MRI * Exercise limitation aside from that due to PAD (i.e. COPD, degenerative joint disease, etc.) * Women who are pregnant * Women who are nursing * Primary indications for systemic oral anticoagulation for active arterial or venous thromboembolic disease.