Pericyte Dysfunction Under Hyperglycemic Stress: Molecular Implications in Metabolic Syndrome

Pericytes are multifunctional mural cells essential for maintaining capillary integrity and regulating vascular tone. Under conditions of acute or chronic hyperglycemia, as observed in metabolic syndrome, pericytes show a profound molecular dysfunction. These include oxidative and nitrosative stress, mitochondrial fragmentation, impaired autophagy, and activation of pro-inflammatory transcription factors such as NF-κB. The resulting pericyte dropout contributes to microvascular instability, enhanced vascular permeability, and tissue hypoxia, particularly in vulnerable regions such as the retina, pancreas, and brain. Moreover, hyperglycemia-induced VEGF overexpression further exacerbates angiogenic imbalance and endothelial-pericyte uncoupling. This research synthesizes up-to-date evidence on pericyte vulnerability in metabolic syndrome, highlighting early biomarkers and potential therapeutic targets in preventing microvascular complications.