International Journal of Molecular Sciences · 6 authors, 3 centres
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This in vitro study in human aortic endothelial cells found that acute high glucose exposure for 7 hours causes mitochondrial network fragmentation and dysfunction, reducing respiration parameters. Treatment with PDGF-C partially restored mitochondrial morphology and specifically rescued non-mitochondrial oxygen consumption rate.
Metabolic diseases like diabetes are major risk factors for cardiovascular disease, partly due to endothelial dysfunction. High glucose (HG) levels induce mitochondrial damage and dysfunction in endothelial cells, a key mechanism of endothelial injury. This study used an in vitro model of human aortic endothelial cells (HAECs) treated with 35 mmol/L d-glucose for 7 hours to investigate the impact of acute HG on mitochondrial dynamics and bioenergetics, and the potential protective role of PDGF-C. HG exposure led to mitochondrial network fragmentation, characterized by shorter mitochondria, reduced branching, and altered expression of fusion (decreased OPA1) and fission (increased phosphorylated DRP1) proteins. Functionally, HG decreased multiple mitochondrial respiration parameters, including basal respiration, maximal respiration, and ATP-linked oxygen consumption rate (OCR). Treatment with PDGF-C partially restored mitochondrial morphology by increasing OPA1 expression and reversing the increase in phosphorylated DRP1. However, PDGF-C only significantly recovered the non-mitochondrial OCR parameter. The study demonstrates that acute metabolic stress from high glucose disrupts mitochondrial structure and oxidative phosphorylation in macrovascular endothelial cells. PDGF-C shows promise as a modulator of mitochondrial dynamics, but its effects on bioenergetics were limited in this model. Limitations include the use of a single acute time point and cell line, the lack of functional endothelial outcome measures like nitric oxide production, and the need to verify mechanisms in more complex systems. The findings provide a foundation for further research into targeting mitochondrial pathways to mitigate early diabetic vascular dysfunction.
