2026-10-13T01:20:21Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33967550 2026-09-22T17:40:05Z category_1 category_146 category_7 category_12 category_13 category_14 category_16 category_21 category_734 category_61 category_132 portal_87 item_type_3 month_year_09_2026

γ-Glutamylcysteine alleviates hypertension and vascular remodeling in SHR by suppressing oxidative stress through Keap1 S-glutathionylation Jianzhen Lei (25091261) Yueru Kong (25091264) Chao Ye (765248) Chuanyue Zhang (22845434) Yi Shen (152956) Xin Wu (10164) Qiuyue Wu (298026) Ying Han (137520) Min Chen (147733) Yueqi Song (7255751) Qing Yan (72879) Fen Zheng (10133801) Xinyi Xia (7516694) Biophysics Space Science Medicine Cell Biology Genetics Molecular Biology Physiology Biotechnology Biological Sciences not elsewhere classified Developmental Biology Infectious Diseases γ-Glutamylcysteine hypertension vascular remodeling vascular smooth muscle cells phenotypic switching oxidative stress Nrf2/Keap1 S-glutathionylation <p>Pathological arterial remodeling heavily depends on the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs). This study explores how <i>γ</i>-Glutamylcysteine (<i>γ</i>-GC) regulates VSMC signaling to mitigate hypertensive structural damage.</p> <p>Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats received intraperitoneal injections of <i>γ</i>-GC (100 mg/kg) every two days for 4 weeks. Blood pressure and arterial remodeling were evaluated. Primary aortic VSMCs were cultured for cellular mechanism analysis. To verify Nrf2 pathway requirement, the Nrf2 inhibitor ML385 was applied <i>in vitro</i> and via osmotic pumps <i>in vivo</i>.</p> <p><i>γ</i>-GC lowered systemic blood pressure and prevented arterial medial thickening in SHR, while normotensive controls remained unaffected. In SHR-VSMCs, <i>γ</i>-GC inhibited cell migration, proliferation, and phenotypic switching, and alleviated cellular oxidative stress. RNA-seq revealed significant enrichment of the Nrf2 signaling pathway. Mechanistically, <i>γ</i>-GC induced Keap1 S-glutathionylation, which disrupted the Keap1 and Nrf2 interaction and promoted Nrf2 nuclear translocation. Notably, Nrf2 inhibition with ML385 abolished the protective effects of <i>γ</i>-GC <i>in vivo</i> and <i>in vitro</i>.</p> <p><i>γ</i>-GC attenuates hypertensive arterial remodeling by modulating intracellular signaling, specifically through Keap1 S-glutathionylation-dependent Nrf2 activation. The Keap1/Nrf2 signaling axis is required for <i>γ</i>-GC to restore VSMC function, suggesting a targeted molecular mechanism for cardiovascular protection.</p> 2026-09-22T17:40:05Z Dataset Dataset 10.6084/m9.figshare.33967550.v1 https://figshare.com/articles/dataset/_-Glutamylcysteine_alleviates_hypertension_and_vascular_remodeling_in_SHR_by_suppressing_oxidative_stress_through_Keap1_S-glutathionylation/33967550 CC BY 4.0