Sex differences in vascular aging and impact of GPER deletion

Benard O. Ogola, Caleb M. Abshire, Bruna Visniauskas, Jasmine X. Kiley, Alec C. Horton, Gabrielle L. Clark-Patterson, Isabella Kilanowski-Doroh, Zaidmara Diaz, Anne N. Bicego, Alexandra B. McNally, Margaret A. Zimmerman, Leanne Groban, Aaron J. Trask, Kristin S. Miller, Sarah H. Lindsey

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Aging is a nonmodifiable risk factor for cardiovascular disease associated with arterial stiffening and endothelial dysfunction. We hypothesized that sex differences exist in vascular aging processes and would be attenuated by global deletion of the G protein- coupled estrogen receptor. Blood pressure was measured by tail-cuff plethysmography, pulse wave velocity (PWV) and echocardiography were assessed with high-resolution ultrasound, and small vessel reactivity was measured using wire myography in adult (25 wk) and middle-aged (57 wk) male and female mice. Adult female mice displayed lower blood pressure and PWV, but this sex difference was absent in middle-aged mice. Aging significantly increased PWV but not blood pressure in both sexes. Adult female carotids were more distensible than males, but this sex difference was lost during aging. Acetylcholineinduced relaxation was greater in female than male mice at both ages, and only males showed aging-induced changes in cardiac hypertrophy and function. GPER deletion removed the sex difference in PWV and ex vivo stiffness in adult mice. The sex difference in blood pressure was absent in KO mice and was associated with endothelial dysfunction in females. These findings indicate that the impact of aging on arterial stiffening and endothelial function is not the same in male and female mice. Moreover, nongenomic estrogen signaling through GPER impacted vascular phenotype differently in male and female mice. Delineating sex differences in vascular changes during healthy aging is an important first step in improving early detection and sex-specific treatments in our aging population.

Original languageEnglish (US)
Pages (from-to)H336-H349
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2
StatePublished - Aug 2022
Externally publishedYes


  • GPER
  • arterial stiffening
  • pulse wave velocity
  • sex differences
  • vascular aging

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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