2. Academic Validation
  3. SPARC: a key mediator of apoptosis in human umbilical vein endothelial cells and its role in hypertension mechanism

SPARC: a key mediator of apoptosis in human umbilical vein endothelial cells and its role in hypertension mechanism

  • In Vitro Cell Dev Biol Anim. 2025 Apr;61(4):374-388. doi: 10.1007/s11626-025-01026-1.
Yingyue Zhang # 1 2,  Haijing Zhao # 1 2,  Liuyang Tian # 1 3,  Zengao Yang 1 4,  Li Zheng 1 5,  Honghong Zhang 1 2,  Yue Zhu 1 2,  Yuhan Ma 1 5,  Yong Xu 6 7,  Yuqi Liu 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Cardiology, The Sixth Medical Centre, Chinese PLA General Hospital, Beijing, 100037, P.R. China.
  • 2 Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, 100853, P.R. China.
  • 3 Beijing an Zhen Hospital, Affiliated of Capital University of Medical Sciences, Beijing, 100029, P.R. China.
  • 4 School of Medicine, South China University of Technology, Guangzhou, 510006, P.R. China.
  • 5 School of Medicine, Nankai University, Tianjin, 300071, P.R. China.
  • 6 Department of Cardiology, The Sixth Medical Centre, Chinese PLA General Hospital, Beijing, 100037, P.R. China. 13701141929@163.com.
  • 7 Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, 100853, P.R. China. 13701141929@163.com.
  • 8 Department of Cardiology, The Sixth Medical Centre, Chinese PLA General Hospital, Beijing, 100037, P.R. China. ametuofo980869@163.com.
  • 9 National Key Laboratory of Kidney Diseases, Beijing, 100853, P.R. China. ametuofo980869@163.com.
  • 10 Department of Cardiology & National Clinical Research Center of Geriatric Disease, Beijing, 100853, P.R. China. ametuofo980869@163.com.
  • 11 Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Beijing, 100853, P.R. China. ametuofo980869@163.com.
  • # Contributed equally.
PMID: 40229525 DOI: 10.1007/s11626-025-01026-1
Abstract

Hypertensionis a leading global health issue associated with high mortality and severe complications. Understanding its molecular mechanisms is essential for identifying novel therapeutic targets. Secreted protein acidic and rich in cysteine (SPARC) is associated with cell migration, disease pathophysiology, and inflammation; however, its role in hypertension remains under investigation. This study investigates the role of SPARC in hypertension, focusing on its impact on endothelial dysfunction.Using the GSE75815 dataset from the GEO database, we identified 71 differentially expressed genes (DEGs) associated with hypertension. Pathway analyses and protein-protein interaction networks constructed through the STRING database highlighted six hub genes, with further evaluation based on Comparative Toxicogenomics Database (CTD) scores. Immune cell profiling via ImmuCellAI revealed an increase in naive B cells, positively correlating with hub gene expression.Experimental validation in human umbilical vein endothelial cells (HUVECs) treated with angiotensin II demonstrated that SPARC downregulation reduced Apoptosis and Bax expression. Silencing SPARC enhanced endothelial cell proliferation, migration, and nitric oxide production, counteracting angiotensin II-induced damage. Notably, angiotensin II upregulated SPARC secretion, suggesting its critical role in mediating endothelial dysfunction.These findings establish SPARC as a key contributor to the molecular pathways underlying hypertension. Targeting SPARC may represent a novel therapeutic strategy to mitigate endothelial dysfunction and improve outcomes for hypertensive patients.Our findings highlight SPARC as a key player in the molecular pathways of hypertension. Modulating SPARC expression may offer a promising therapeutic strategy to counteract endothelial dysfunction and improve outcomes in hypertensive patients.

Keywords

SPARC (secreted protein acidic and rich in cysteine); Angiotensin II; Apoptosis; Bioinformatics; HUVEC; Hypertension; Immunity.

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