A5034704021- Extracellular vesicles in disease
- Cerebrovascular and Carotid Artery Diseases
- Neurological Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Nitric Oxide and Endothelin Effects
- Neurological Disorders and Treatments
- Acute Ischemic Stroke Management
- S100 Proteins and Annexins
- Circular RNAs in diseases
- Eicosanoids and Hypertension Pharmacology
- Adipose Tissue and Metabolism
- Trace Elements in Health
- Neurogenetic and Muscular Disorders Research
- Hydrogen's biological and therapeutic effects
- Cancer-related molecular mechanisms research
- Cancer, Hypoxia, and Metabolism
- Cerebrovascular and genetic disorders
- Cardiovascular Health and Disease Prevention
- Ferroptosis and cancer prognosis
- Venous Thromboembolism Diagnosis and Management
- Pharmacological Effects and Toxicity Studies
- Cardiovascular Disease and Adiposity
- Renin-Angiotensin System Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Diagnosis and Treatment of Venous Diseases
Medical University of South Carolina
2023-2025
Ralph H. Johnson VA Medical Center
2024
Charlie Norwood VA Medical Center
2022
Augusta University
2019-2022
Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate consequences MI are a high priority. Cardiac progenitor cells (CPCs) have been used treat cardiac injury post-MI, despite poor engraftment, they shown inhibit apoptosis promote angiogenesis through poorly understood paracrine effects. We previously reported that direct injection exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against in...
Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) exhibit detrimental effects. Exercise improves endothelial function in part via the secretion exosomes into circulation. Extracellular superoxide dismutase (SOD3) is a major secretory copper (Cu) antioxidant enzyme that catalyzes dismutation O2•- to H2 O2 whose activity requires Cu transporter ATP7A. However, role SOD3 exercise-induced angiogenic effects circulating plasma on cells (ECs) T2DM...
Introduction: Cerebrovascular pathologies leading to VCID are diverse, but preclinical models mainly rely on chronic hypoperfusion-mediated neuroinflammation in otherwise healthy animals. Since diabetes increases risk, our first goal was develop a multi-etiology model of diabetes. Given that endothelin-1 (ET-1) contributes decreased cerebral blood flow multiple dementia and ETAR-mediated senescence brain microvascular endothelial cells, second assess ETARs this model. Methods: Control...
Diabetes increases the risk of Vascular Contributions to Cognitive Impairment&Dementia (VCID) and stroke further amplifies this effect. also dysregulates Endothelin (ET) system. Elevated brain ET-1 levels correlate with tissue perfusion status disease severity in patients ADRD. There is emerging evidence that ETB receptor agonism improves outcomes cerebral ischemic stroke, but long-term effects, especially diabetes, are unknown. Therefore, we hypothesized intranasal treatment ETA...
Diabetes doubles the risk of VCID but underlying reasons remain unclear. Given that diabetes mediates early endothelial dysfunction and activates ET system, post-mortem brain ET-1 levels correlate with tissue hypoxia disease severity in patients dementia, microemboli (ME) are more common diabetic individuals, goals current study were to investigate 1) relationship between neuroinflammation a clinically relevant model VCID, 2) impact improving function on system. At 10 weeks after onset...
Diabetes doubles the risk of VCID. The underlying reasons are not understood, and preventive therapeutic strategies lacking. We showed that diabetic but control rats develop a progressive cognitive decline in microemboli (ME) model Given cerebrovascular dysfunction is common pathology between diabetes VCID, we hypothesized improvement endothelial function prevents ME-mediated impairment. Our treatment paradigm was based on recently reported LACI-2 Trial which assessed efficacy isosorbide...
Both female sex and diabetes increase the risk of poor stroke recovery, but underlying mechanisms are unclear. We reported that inhibition MMP3 with UK356618 prevents hemorrhagic transformation (HT) in male diabetic rats, rats develop greater HT than males. Emerging evidence suggests may contribute to regulation EndMT, a process associated scarring impaired healing. tested hypotheses that: 1) activity is amplified extent cerebrovasculature especially after stroke; 2) EndMT occurs brain...
Diabetes increases the risk of hemorrhagic transformation as well post-stroke cognitive impairment (PCSI). We have shown that iron chelation in subacute phase improves stroke outcomes experimental models diabetes. hypothesized inhibition ferroptosis, iron-induced cell death, period will prevent PSCI diabetic animals. Methods: Male rats, housed reverse light cycle, underwent sham or 60-min middle cerebral artery occlusion surgery 8 weeks after diabetes onset. After MRI, rats met preset...
Background: Exercise restores decreased capillary density in skeletal muscle (SKM) (capillary rarefaction) type2 diabetes (T2D) that has eNOS uncoupling/excess O 2 - , which is required for treatment of diabetic peripheral vascular disease (PAD) via unknown mechanisms. AMP-activated protein kinase (AMPK) a key angiogenic/metabolic mainly regulated by phosphorylation and baseline, but not exercise-induced SKM under healthy conditions. AMPK senses H signal to increase its activity oxidative...
Background Exosomes, a key player in cell‐cell communication, derived from diabetic animals/cells have detrimental effects. Exercise training has beneficial effects to improve endothelial dysfunction metabolic disease such as diabetes mellitus (DM), but its mechanisms are poorly understood. Extracellular superoxide dismutase (ecSOD) is major secretory copper (Cu) containing antioxidant enzyme the vasculature that catalyzes dismutation of O 2 − H and full activity requires Cu transporter...
Background: Exercise training promotes vascular adaptation (restoration of endothelial function and angiogenesis) in type2 diabetes (T2D). Since eNOS uncoupling/O 2 - are increased T2D, exercise may promote via mechanism other than eNOS-NO axis. Extracellular superoxide dismutase (ecSOD) is a secreted copper (Cu) containing SOD that catalyzes the dismutation O to H its full activity requires Cu transporter ATP7A. We reported ATP7A-ecSOD pathway reduced T2D ecSOD-derived VEGFR2 signaling...
Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation O •- to H its full activity requires transporter ATP7A. We reported ecSOD-derived cells (ECs) enhances...
Background: Exercise training protects against type2 diabetes (T2D)-induced endothelial dysfunction which is mediated through eNOS uncoupling-induced O 2 -, but its underlying mechanisms are not fully understood. Cu transporter ATP7A required for full activity of antioxidant enzyme extracellular SOD (SOD3) that scavenges - to generate H has been proposed function as a signaling molecule mediate endothelium-dependent vasorelaxation (EDR) in T2D instead nitric oxide (NO). However, role and...