Abstract
Atherosclerosis is the primary cause of several cardiovascular diseases. Oxidized low-density lipoprotein (ox-LDL)-induced apoptosis, endothelial–mesenchymal transition (EndMT), and inflammation are crucial for the progression of cardiovascular diseases, including atherosclerosis. Naringin, a major compound from tomatoes, grapefruits, and related citrus, reportedly exhibits potential protective effects during atherosclerosis development; however, its effect on ox-LDL-induced human umbilical vein endothelial cell (HUVEC) damage remains unknown. In the present study, we investigated the anti-apoptotic and anti-inflammatory activities of naringin against ox-LDL-induced endothelial cells, and the underlying mechanism. Naringin pretreatment significantly and concentration-dependently inhibited ox-LDL-induced cell injury and apoptosis. Additionally, naringin restored endothelial barrier integrity by preventing VE-cadherin disassembly and F-actin remodeling, and down-regulated pro-inflammatory factors like IL-1β, IL-6, and IL-18, in the HUVECs. We also demonstrated that naringin treatment restored ox-LDL-induced YAP (yes-associated protein) down-regulation, given the YAP-shRNA attenuated cytoprotective effect of naringin on ox-LDL-induced endothelial cell injury and apoptosis. Collectively, our data indicate that naringin reversed ox-LDL-triggered HUVEC apoptosis, EndMT, and inflammation by inhibiting the YAP pathway. Therefore, naringin may have a therapeutic effect on endothelial injury-related disorders.
Highlights
Atherosclerosis is the predominant cause of cardiovascular diseases, and is becoming a global concern, owing to its high prevalence [1]
It is commonly thought that endothelial cell injury and apoptosis are the basis and initial steps in the pathogenesis of atherosclerosis [19]
Chemical stress from harmful substances such as cytokines and oxidized lipids, are known to be key players in endothelial cell injury [8]. Oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury is considered a crucial contributor to the pathogenesis and progression of atherosclerosis [20]
Summary
Atherosclerosis is the predominant cause of cardiovascular diseases, and is becoming a global concern, owing to its high prevalence [1]. Endothelial injury and apoptosis are the main pathological processes of atherosclerosis, known to trigger thrombosis and accelerate atherosclerotic plaque formation [2]. The arterial deposition of ox-LDL cholesterol is closely associated with atherosclerosis-related morbidity [3]. Accumulating evidence indicate the common occurrence of endothelial–mesenchymal transition (EndMT) in atherosclerosis [4]. EndMT is characterized by specific endothelial marker loss, and mesenchymal marker acquisition [5]. The loss of morphological and functional vascular endothelial cell integrity is closely related to cell inflammation and apoptosis in atherosclerosis [6,7]. Ox-LDL promotes the formation and development of atherosclerotic plaques, by inducing vascular endothelial inflammation and apoptosis [8]. Therapeutic strategies against vascular endothelial cell EndMT, inflammation, and apoptosis may lead to the remission of endothelial-related pathology [9]
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