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Endothelial Dysfunction with Aging: Does Sex Matter?

Jakub Jozue Wojtacha1, Barbara Morawin1, Edyta Wawrzyniak-Gramacka1

  • 1Department of Applied and Clinical Physiology, University of Zielona Gora, 28 Zyty Str., 65-417 Zielona Gora, Poland.

International Journal of Molecular Sciences
|November 27, 2024
PubMed
Summary

This study reveals sex-specific differences in oxidative stress and inflammation markers in older adults, impacting vascular disease risk. Understanding these sex-specific oxi-inflammatory responses is crucial for predicting and preventing cardiovascular events in aging populations.

Keywords:
3-nitrotyrosineblood cell countendothelial progenitor cellsnitric oxideolder adultssystemic inflammatory index

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Area of Science:

  • Gerontology and Cardiovascular Research
  • Biochemistry of Oxidative Stress and Inflammation
  • Sex-Based Differences in Health

Background:

  • Endothelial dysfunction in older adults is linked to oxidative stress and inflammation from excessive reactive oxygen and nitrogen species (RONS).
  • Existing research often overlooks sex-specific variations in these physiological processes, potentially limiting effective vascular disease prediction and prevention strategies.
  • Understanding the interplay of RONS, inflammation, and endothelial health is critical for addressing cardiovascular risks in aging populations.

Purpose of the Study:

  • To investigate the utility of serum oxi-inflammatory markers for predicting and preventing vascular disease, with a specific focus on sex differences.
  • To elucidate the distinct mechanisms of oxidative stress and inflammation in older women and men.
  • To identify reliable sex-specific biomarkers for assessing endothelial dysfunction and cardiovascular risk.

Main Methods:

  • Analysis of serum samples from 145 women and 50 men (mean age 72.2 ± 7.8 years) for hydrogen peroxide (H2O2), nitric oxide (NO), and 3-nitrotyrosine (3-NitroT) levels.
  • Assessment of sex-specific correlations between NO/3-NitroT ratios and endothelial dysfunction.
  • Evaluation of inflammation-specific variables (neutrophil-to-lymphocyte ratio, systemic immune inflammation index, neutrophil-to-HDL ratio, CRP-to-HDL ratio) and their diagnostic utility.

Main Results:

  • Older women showed elevated H2O2 and NO production, with reduced NO bioavailability (high 3-NitroT), indicating sex-specific endothelial dysfunction.
  • The NO/3-NitroT relationship differed significantly between sexes (women: rs = 0.811; men: rs = -0.611), highlighting sex as a determinant of endothelial dysfunction.
  • Women exhibited increased circulating progenitor cells, suggesting simultaneous endothelial regeneration, and reduced inflammation markers, with CRP-to-HDL ratio showing high diagnostic utility (AUC = 0.980).

Conclusions:

  • This study is the first to demonstrate sex-specific changes in oxi-inflammatory responses contributing to vascular dysfunction in older adults.
  • Sex-specific biomarkers, particularly the C-reactive-protein-to-HDL ratio, can effectively predict clinical prognosis in vascular dysfunction.
  • These findings underscore the importance of considering sex in the assessment and management of cardiovascular disease risk in aging individuals.