Abstract
Endothelial injury plays a critical role in the pathogenesis of cardiovascular disorders and metabolic-associated vascular complications which are the leading cause of death worldwide. However, the mechanism underlying endothelial dysfunction is not completely understood. The study is aimed at investigating the role of tubulin polymerization-promoting protein family member 3 (TPPP3) in palmitic acid- (PA-) induced endothelial injury. The effect of TPPP3 on human umbilical vein endothelial cells (HUVECs) was determined by evaluating apoptosis, tube formation, and reactive oxygen species (ROS) production. TPPP3 silencing inhibited PA overload-induced apoptosis and production of ROS, along with the alteration of apoptosis-related key proteins such as BCL-2 and Bax. Mechanically, voltage-dependent anion channel 1 (VDAC1) was identified as a novel functional binding partner of TPPP3, and TPPP3 promoted VDAC1 protein stability and its activity. Further studies indicated that TPPP3 could promote apoptosis, ROS production, tube formation, and proapoptotic protein expression and reduce antiapoptotic protein expression through increasing VDAC1 expression under mildly elevated levels of PA. Collectively, these results demonstrated that TPPP3 could promote PA-induced oxidative damage in HUVECs via a VDAC1-dependent pathway, suggesting that TPPP3 might be considered as a potential therapeutic target in vascular disease.
Highlights
Vascular disease is the top cause of mortality and disability worldwide
To assess the effect of lipid disorders on the expression of tubulin polymerization-promoting protein family member 3 (TPPP3) in human umbilical vein endothelial cells (HUVECs), HUVECs were treated with different concentrations of Palmitic acid (PA)
These results demonstrated that PA was able to induce lipotoxicity, accompanied by the increase of TPPP3
Summary
Vascular disease is the top cause of mortality and disability worldwide. Impairment of endothelial function may have dramatically contributed to the initiation and development of vascular diseases [1, 2]. Endothelial dysfunction involves the pathogenesis of various cardiovascular events and vascular complications of diabetes and is the starting point of these diseases [3,4,5]. The protection of endothelial function has a potential benefit for cardiovascular disorder and diabetic vascular complications. Increasing evidence shows that high levels of reactive oxygen species- (ROS-) induced oxidative stress is a critical pathogenic factor in endothelial cell injury [6, 7]. Metabolic stress resulting from increased FFAs gives rise to endothelial dysfunction and apoptosis [10, 11], which promotes atherosclerosis and other cardiovascular diseases. The exact mechanism of how lipid disorders cause endothelial injuries remains to be defined
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