Plasma Sestrin2 levels and risk of acute ischemic stroke: A case–control study

Loulia Bader; Aijaz Parray; Naveed Akhtar; Hicham Raïq; Sajitha V. Pananchikkal; Raheem Ayadathil; Deborah M. Morgan; Blessy Babu; Reny Francis; Ahmed Own; Ghulam Jeelani Pir; Ashfaq Shuaib; Abdelali Agouni

doi:10.17305/bb.2025.12367

Authors

Loulia Bader Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar
Aijaz Parray Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Naveed Akhtar Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Hicham Raïq Department of Social Sciences, College of Arts and Sciences, Qatar University, Doha, Qatar
Sajitha V. Pananchikkal Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar https://orcid.org/0000-0002-1045-8854
Raheem Ayadathil Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Deborah M. Morgan Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Blessy Babu Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Reny Francis Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Ahmed Own Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Ghulam Jeelani Pir Neuroscience Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
Ashfaq Shuaib Department of Medicine (Neurology), University of Alberta, Edmonton, Canada
Abdelali Agouni Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar

DOI:

https://doi.org/10.17305/bb.2025.12367

Keywords:

Sestrin2, acute ischemic stroke, ischemia, nitric oxide, total antioxidant capacity

Abstract

Sestrin2, a stress-inducible protein with antioxidant properties, is upregulated in response to various stressors, including oxidative and energetic stress. This study examines the relationship between plasma Sestrin2 levels, total antioxidant capacity (TAC), total nitric oxide (NO), and the likelihood of experiencing an acute ischemic stroke (AIS) within the Qatari population. The cohort consisted of 187 AIS patients and 30 healthy controls. Plasma concentrations of Sestrin2, TAC, and nitrite/nitrate (an indirect measure of NO) were evaluated at four intervals: within 48 hours of stroke onset, and at 5 days, 30 days, and 1 year post-stroke. At stroke onset, AIS patients exhibited significantly lower plasma levels of Sestrin2 (1.434±3.57 vs. 8.383±7.39; p <0.001), TAC (1.88±0.42 vs. 2.279±0.326; p <0.001), and nitrite/nitrate (53.5±47.9 vs. 65.951±44.07; p = 0.04) compared to controls. Sestrin2 levels remained diminished at 5 and 30 days post-stroke, while NO levels increased by day 5 (p = 0.01). Multiple logistic regression analysis revealed that male sex, diabetes, high National Institutes of Health Stroke Scale (NIHSS) scores, and small vessel disease (SVD) were associated with increased odds of AIS, whereas Middle Eastern ethnicity correlated with reduced odds. Notably, higher tertiles of Sestrin2, TAC, and NO were linked to decreased odds of AIS, with adjusted odds ratios of 0.123 (p < 0.001), 0.327 (p = 0.01), and 0.063 (p = 0.01), respectively. The observed lower plasma levels of Sestrin2, TAC, and NO at stroke onset and up to 30 days post-event suggest their potential role as biomarkers in stroke occurrence and recovery, with elevated levels associated with a decreased likelihood of AIS.

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