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Full text release has been delayed at the author's request until May 17, 2026

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Interaction Between Aging, Ovarian Hormones, and Elastin Haploinsufficiency on Cardiovascular Regulation by the Kidney

Dixon, Alethia J
http://orcid.org/0000-0002-4374-0688
http://rave.ohiolink.edu/etdc/view?acc_num=case1706193500276257

Abstract Details

2024, Doctor of Philosophy, Case Western Reserve University, Physiology and Biophysics.
Functional elastin fibers within extracellular matrix of the arterial wall facilitate passive distensibility and recoil, which is critical to maintaining blood flow. Elastin fragmentation decreases functional elastin level and is associated with aging, contributing to age-related arterial stiffening, an independent risk factor for the development of hypertension. The effects of elastin deficiency in large elastic vessels are well-known, but the impact on resistance vessels, crucial for renal perfusion and blood pressure regulation, is less explored. Furthermore, elastin insufficiency in mice is associated with elevated blood pressure, which is more pronounced in male mice than female mice when compared to their respective wild-type counterparts. However, the mechanisms underlying the sex-related differences in elastin-insufficient mice have not been explored. Using an animal model of elastin haploinsufficiency (Eln+/-), we demonstrated that loss of elastin exacerbates structural and biomechanical properties of intra-renal arteries in young Eln+/- female mice. These changes manifest as increased vascular stiffness and increased fragmentation, leading to blunted responses to increased renal perfusion pressure and impaired renal autoregulation. We further explored whether renal dysfunction contributes to hypertension in these mice and whether this relationship is modulated by ovarian hormones. Our findings establish that ovarian hormones mitigate the hypertensive phenotype in female Eln+/- mice. Though these mice exhibit impaired pressure natriuresis response, the hypertensive phenotype is not sodium-dependent. Instead, the sustained elevation in blood pressure is in part driven by increased activity of the renin-angiotensin system (RAS). Additionally, diuresis and urine concentrating ability were found to be impaired in female Eln+/- mice despite increased aquaporin 2 channel expression. Furthermore, the reduced sensitivity to vasopressin (V2) receptor blockade in Eln+/- mice and normal copeptin levels revealed an altered vasopressin mechanism that may potentially be responsible for increased fluid retention and sustained hypertension. Overall, our results establish that elastin insufficiency accelerates age-related renal dysfunction due to renal vasculature remodeling. Additionally, ovarian hormones play a role in dampening blood pressure elevation in female Eln+/- mice, which is partly due to increased RAS and an altered vasopressin system that favors increased sodium and water reabsorption.
Patrick Osei-Owusu (Advisor)
George Dubyak (Committee Chair)
Jessica Wagenseil (Committee Member)
Julian Stelzer (Committee Member)
Jeffery Garvin (Committee Member)
Physiology
Extracellular matrix, cardiovascular disease, hypertension, renal dysfunction, vascular physiology, renal hemodynamics

Recommended Citations

Citations

  • Dixon, A. J. (2024). Interaction Between Aging, Ovarian Hormones, and Elastin Haploinsufficiency on Cardiovascular Regulation by the Kidney [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1706193500276257

    APA Style (7th edition)

  • Dixon, Alethia. Interaction Between Aging, Ovarian Hormones, and Elastin Haploinsufficiency on Cardiovascular Regulation by the Kidney. 2024. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1706193500276257.

    MLA Style (8th edition)

  • Dixon, Alethia. "Interaction Between Aging, Ovarian Hormones, and Elastin Haploinsufficiency on Cardiovascular Regulation by the Kidney." Doctoral dissertation, Case Western Reserve University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1706193500276257

    Chicago Manual of Style (17th edition)

case1706193500276257
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.