Date of Award

12-2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Engineering and Sciences

First Advisor

Kenia Pedrosa Nunes

Second Advisor

Toby S. Daly-Engel

Third Advisor

Charles Polson

Fourth Advisor

Jianhui Li

Abstract

Vascular dysfunction is a key feature of hypertension and is associated with altered calcium (Ca2+) handling. Since cytosolic Ca2+ levels regulate vascular tone, maintaining their homeostasis is essential for vascular function. Heat Shock Protein 70 (HSP70) is a molecular chaperone that has emerged as an important regulator in vascular biology, supporting smooth muscle contraction by modulating Ca2+ dynamics. Interestingly, its biological effects differ depending on its cellular localization. HSP70 levels and function within the vasculature may also be altered by physiological factors, including sex and age, and have also been linked to pathological conditions such as diabetes. However, its role in hypertension-associated vascular dysfunction is unclear. Still, whether HSP70-mediated mechanisms are affected by sex as a biological variable remains unknown. Using complementary approaches, our findings demonstrate thatHSP70 contributes to abnormal vascular contractility by regulating Ca2+ dependent signaling in a sex dependent manner during hypertension. Collectively, these results provide a mechanistic understanding of HSP70's role in mediating vascular responses and identify it as a potential target for mitigating damage in blood vessels induced by hypertension.

Available for download on Wednesday, December 12, 2029

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