Test the theory that abnormalities in the large blood vessels that deliver blood to your leg and the very small blood vessels in your leg's muscles (invisible to the eye) work together to worsen your leg function and walking.

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.