Diabetes-Induced Vascular Dysfunction and Stemness Decline Investigated via Transcription Factor-Driven Genetic Switches

AbstractBackground:Diabetes mellitus precipitates cardiovascular complications through hyperglycemia, oxidative stress, and inflammation, disrupting vascular cell function. This dysfunction involves altered regulation of transcription factors like Nrf2 and FOXP1, leading to endothelial dysfunction, impaired angiogenesis, and faulty vascular remodeling. Additionally, diabetes reduces the stemness of vascular progenitor cells, hampering vascular repair and homeostasis. Understanding these mechanisms is crucial for identifying therapeutic targets to mitigate diabetic vascular complications.Methods:Databases, including PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals were searched for published articles without any date restrictions, to investigate the diabetes-induced vascular dysfunction and stemness decline through the lens of vascular transcription factor-driven genetic switches. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate how diabetes harms vascular cells. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).Results:This study reveals significant dysregulation of key transcription factors including Nrf2, FOXP1, SMAD, PAX3/7, and GATA in diabetes, leading to compromised oxidative stress responses and increased inflammatory signaling in vascular cells. In endothelial cells, impaired function of these factors resulted in decreased nitric oxide production and increased endothelial permeability. Additionally, altered FOXP1 and GATA activity exacerbated vascular inflammation. In VSMCs, diabetes-induced transcription factor dysregulation promoted a shift from a contractile to a synthetic phenotype, characterized by increased proliferation and matrix production, contributing to vascular stiffness and atherosclerosis. The stemness of vascular progenitor cells was notably reduced, affecting their differentiation capabilities and exacerbating vascular complications in diabetic conditions.Conclusion:Diabetes impairs vascular health by disrupting key transcription factors and signaling pathways, leading to endothelial dysfunction, abnormal vascular remodeling, and a decline in stemness of vascular cells. Dysregulated factors like Nrf2, FOXP1, and GATA contribute to reduced nitric oxide production, increased vascular permeability, and enhanced inflammation, exacerbating atherosclerosis and hypertension. Addressing these dysfunctions through targeted therapies that enhance transcription factor activity and modulate signaling pathways may mitigate diabetes-related vascular complications. Further research is essential for developing effective interventions to restore vascular homeostasis in diabetic patients.