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The vascular endothelium plays a critical role in maintaining cardiovascular homeostasis by releasing vasoactive mediators, regulating blood flow, controlling vascular growth, and maintaining the balance between coagulation and fibrinolysis.
Loxoprofen sodium protects HUVEC endothelial cells from angiotensin II–induced injury by reducing ROS production, restoring mitochondrial membrane potential, and suppressing apoptosis through regulation of Bax, Bcl-2, and caspase-3.
The vascular endothelium plays a critical role in maintaining cardiovascular homeostasis by releasing vasoactive mediators, regulating blood flow, controlling vascular growth, and maintaining the balance between coagulation and fibrinolysis. Impairment of endothelial function is strongly linked with oxidative stress and arterial stiffness, key contributors to cardiovascular disease. This study investigated the protective effects of loxoprofen sodium on angiotensin II–induced endothelial injury in human umbilical vein endothelial cells (HUVECs).
An in vitro endothelial cell injury model was developed by exposing HUVECs to angiotensin II. The expression of key molecular markers implicated in oxidative stress and apoptosis—including angiotensin II type 2 receptor (AT2R), nicotinamide adenine dinucleotide phosphate oxidase (NOX)-4, B-cell lymphoma 2 (Bcl-2), Bcl-2–associated X protein (Bax), and caspase-3—was analyzed using quantitative real-time polymerase chain reaction and western blotting.
Intracellular reactive oxygen species (ROS) levels were measured with the dichlorodi-hydrofluorescein diacetate (DCFH-DA) assay, while reduced glutathione (GSH) concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (MMP) was checked through the dihydrorhodamine 123 assay. Cell viability and proliferation were determined using methylthiazolyl tetrazolium (MTT) assays, and lactate dehydrogenase (LDH) release was evaluated as a marker of cellular injury. Flow cytometry was performed to quantify apoptosis in HUVECs.
Treatment with loxoprofen sodium substantially inhibited the angiotensin II–induced increase in endothelial AT2R expression. The drug also reduced oxidative stress, evidenced by decreased ROS production and downregulation of NOX-2 and NOX-4, while restoring GSH levels. In addition, loxoprofen improved mitochondrial membrane potential, enhanced endothelial cell viability, and reduced LDH release, indicating protection against cellular damage. Notably, loxoprofen attenuated endothelial apoptosis by modulating key apoptotic regulators, restoring the balance between pro-apoptotic Bax and anti-apoptotic Bcl-2, and reducing caspase-3 activation.
Loxoprofen sodium protects endothelial cells from angiotensin II–induced oxidative stress and apoptosis, highlighting its potential role in preventing endothelial dysfunction and vascular injury associated with cardiovascular diseases.
Drug Design, Development and Therapy
Loxoprofen Sodium Alleviates Oxidative Stress and Apoptosis Induced by Angiotensin II in Human Umbilical Vein Endothelial Cells (HUVECs)
Chuanzhao Ji et al.
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