Curcumin rescues HSP70 profile in type 1 diabetes and mitgates aortic vascular dysfunction

Background: Type 1 diabetes (T1D) is associated with vascular dysfunction, driven by hyperglycemia, calcium (Ca 2+ ) mishandling, enhanced vasoconstriction, and aortic wall changes. Heat Shock Protein 70 (HSP70) is a molecular chaperone present intracellularly (iHSP70) and extracellularly (eHSP70) in circulation. iHSP70 is cytoprotective, and regulates the vasculature by handling Ca 2+ , whereas eHSP70 acts as a pro-inflammatory. Importantly, an imbalance between iHSP70 and eHSP70 contributes to vascular dysfunction. Curcumin, a natural polyphenol derived from Curcuma longa (turmeric), exhibits broad pharmacological properties, well-known for treating various cardiovascular conditions. However, whether curcumin restores the eHSP70-iHSP70 balance and Ca 2+ dynamics in the aorta under diabetes remains unclear. Hypothesis: We hypothesized that chronic curcumin treatment modulates HSP70 expression, thereby restoring the eHSP70-iHSP70 balance, normalizing Ca 2+ mishandling, and ameliorating aortic structural and functional alterations in T1D. Methodology: Diabetes was induced in Male-Sprague Dawley rats (6-7 weeks) using a single dose of streptozotocin (STZ; 65 mg/kg, ip). Control (CTL) animals received an equal volume of citrate buffer. Animals were randomly assigned to receive treatment with curcumin (300 mg/kg, orally) for 28 days. Aortic iHSP70 levels were assessed by Western Blotting, while systemic eHSP70 levels were assessed using Western Blotting and ELISA. The eHSP70-iHSP70 ratio was derived from densitometric values. H-index, an indirect marker of low-grade inflammation, was determined. Vascular function was evaluated using a wire myograph in the isolated aorta. An established Ca 2+ protocol was employed to determine Ca 2+ dynamics as a function of the change in force development. Aortic wall remodeling was characterized by confocal microscopy. Results: Chronic treatment with curcumin increased aortic iHSP70 and reduced systemic eHSP70 levels, thereby restoring the eHSP70-iHSP70 ratio in diabetic animals to control levels. The enhanced inflammatory status associated with diabetes was significantly reduced, as reflected by the H-index. Curcumin diminished force development in phasic and tonic contraction components of the vascular biphasic curve by attenuating abnormal Ca 2+ efflux and influx in the aorta. Vascular structural analysis further showed that curcumin reduces collagen deposition and restores elastin levels, improving the elastin-collagen ratio. Conclusion: Curcumin rescues the HSP70 profile by stabilizing the eHSP70-iHSP70 ratio, improves Ca 2+ handling and vascular function in T1D. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.