Background And Aims: Secreted protein acidic and rich in cysteine (SPARC) is involved in the pathological processes of many metabolic diseases. However, studies on the relevance of SPARC to hypertension and its involvement in endothelial function are scarce. In this study, we aim to explore the relevance of SPARC to hypertension and investigate its role in endothelium-dependent relaxation (EDR).
Methods: 110 patients who met the criteria were recruited as participants. Serum SPARC concentrations were determined by Luminex assay. The correlation between SPARC levels and hypertension was analyzed. After treatment with SPARC ex vivo or in vivo, endothelial-dependent relaxation (EDR) was measured by wire myography. Western blotting was performed to detect the expression of proteins relevant to endothelial function.
Results: Our results showed that serum SPARC levels were significantly higher in the hypertensive group and were positively associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Functional results demonstrated that SPARC dramatically impaired EDR and induced the excess production of reactive oxygen species (ROS) in endothelial cells. Further experimental results confirmed that SPARC reduced angiotensin-converting enzyme 2 (ACE2) expression and ACE2 overexpression or activation completely abolished the impairing effect of SPARC on endothelial function.
Conclusions: The present study reveals the correlation between elevated SPARC and hypertension and confirms its adverse effect on endothelial function, helping establish a comprehensive understanding of hypertension-related endothelial dysfunction in a new scope.
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http://dx.doi.org/10.1016/j.atherosclerosis.2023.117390 | DOI Listing |
J Clin Hypertens (Greenwich)
December 2024
Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling Cardiovascular Diseases, Ministry of Education; Collaborative Innovation Center for Cardiovascular Disorders, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, China.
Br J Cancer
November 2024
Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Am J Physiol Heart Circ Physiol
November 2024
Department of Pharmacology, Educational Foundation of Osaka Medical and Pharmacological University, Takatsuki, Japan.
Mol Neurobiol
July 2024
Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke.
View Article and Find Full Text PDFNeoplasia
July 2024
Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Centre Goettingen, Robert-Koch-Straße 40, 37075 Goettingen, Germany; Clinical Research Unit KFO5002, University Medical Center Goettingen, Goettingen, Germany. Electronic address:
Background: Pancreatic ductal adenocarcinoma (PDAC) poorly responds to antineoplastic agents. Discrepancies between preclinical success and clinical failure of compounds has been a continuous challenge and major obstacle in PDAC research.
Aim: To investigate the association of the tumor microenvironment (TME) composition and gemcitabine metabolizing enzyme (GME) expression in vitro and several in vivo models.
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