Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease

Inclusion Criteria: Peripheral artery disease (PAD) participants: * Able to provide written informed consent * 50-75 years of age * Diagnosed as Fontaine stage II-III * History of exercise-induced claudication * Females must be postmenopausal (cessation of menses for \> 24 months) * Normal renal function (serum creatinine-estimated glomerular filtration rate \>= 60 mL/min) or evidence of stable renal function within the last 6 months * Normal hepatic function (alanine transaminase \< 87.5 U/L, alkaline phosphatase \< 260 U/L, total bilirubin 1.8 mg/dL) or evidence of stable hepatic function within the last 6 months * Complete blood count: * Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count \> 700 million lymphocytes/L, or evidence of stable blood counts within the last 6 months * Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count \> 700 million lymphocytes/L, or evidence of stable blood counts within the last 6 months Age-matched control participants: * Able to provide written informed consent * 50-75 years of age * No evidence of peripheral occlusive disease (ankle-brachial index \> 0.90) * Females must be postmenopausal (cessation of menses for \> 24 months) * Normal renal function (serum creatinine-estimated glomerular filtration rate \>= 60 mL/min), or evidence of stable renal function within the last 6 months * Normal hepatic function (alanine transaminase \< 87.5 U/L, alkaline phosphatase \< 260 U/L, total bilirubin 1.8 mg/dL ), or evidence of stable hepatic function within the last 6 months * Complete blood count: * Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count \> 700 million lymphocytes/L * Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count \> 700 million lymphocytes/L, or evidence of stable blood counts within the last 6 months Exclusion Criteria: Peripheral artery disease (PAD) participants: * • Pain at rest and/or tissue loss due to PAD (Fontaine stage IV PAD) * Acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma * Limited walking capacity from conditions other than PAD * No physical exam to assess exercise limitations in the past year * Currently pregnant or nursing * Blood work and medical history NOT demonstrating: * Normal renal function (serum creatinine-estimated glomerular filtration rate \>\> 60 mL/min) * Normal hepatic function (alanine transaminase 0-35 IU/L, alkaline phosphatase 30-120 IU/L, total bilirubin 2-17 micromoles/L), * Diagnosis of multiple sclerosis or psoriasis * Diagnosis of gastrointestinal disorders (e.g., moderate IBS, Crohn's disease, etc. * Concomitant use of dimethyl fumarate * Hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients of VUMERITY * Ulcers, gangrene, or necrosis of the foot (Fontaine stage IV PAD) * Complete blood count NOT within ranges: * Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count 1-4.8 billion lymphocytes/L * Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count 1-4.8 billion lymphocytes/L Age-matched control participants: * Positive diagnosis of PAD * No physical exam to assess exercise limitations in the past year * Any exercise limitations as determined at last physical exam * Limited walking capacity from musculoskeletal injury * Currently pregnant or nursing * Renal function not within normal ranges (serum creatinine-estimated glomerular filtration rate \>\> 60 mL/min) * Hepatic function not within normal ranges (alanine transaminase 0-35 IU/L, alkaline phosphatase 30-120 IU/L, total bilirubin 2-17 micromoles/L) * Complete blood count NOT within ranges: * Females: red blood cell 4-5 trillion cells/L, hemoglobin 12-15 g/dL, hematocrit 34-45%, white blood cell count 3-10 billion cells/L, platelet count 160-380 billion/L, and normal lymphocyte count 1-4.8 billion lymphocytes/L * Males: red blood cell 4-6 trillion cells/L, hemoglobin 13-17 g/dL, hematocrit 38-49%, white blood cell count 3-10 billion cells/L, platelet count 135-320 billion/L, and normal lymphocyte count 1-4.8 billion lymphocytes/L