Affiliation:
1. From the Departments of Pharmacology (H.K.S., K.Y.K., J.H.L., K.W.H.) and Internal Medicine (Y.K.K.), College of Medicine, Pusan National University, Busan, Korea.
Abstract
Background—
Remnant lipoprotein particles (RLPs), products of lipolytic degradation of triglyceride-rich lipoprotein derived from VLDL, exert atherogenesis. In this study, we observed how RLPs induced cytotoxicity in human umbilical vein endothelial cells (HUVECs) and cilostazol prevented cell death.
Methods and Results—
RLPs were isolated from the plasma of hyperlipidemic patients by use of an immunoaffinity gel mixture of anti–apolipoprotein A-1 and anti–apolipoprotein B-100 monoclonal antibodies. RLPs (50 μg/mL) significantly increased superoxide formation in HUVECs associated with elevated gp91phox mRNA and protein expression and Rac1 translocation, accompanied by increased production of tumor necrosis factor (TNF)-α and interleukin-1β, DNA fragmentation, and cell death. Cilostazol (1 to 100 μmol/L) significantly suppressed not only NAD(P)H oxidase–dependent superoxide production but also TNF-α and interleukin-1β release and restored viability. RLPs activated a lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which was not inhibited by cilostazol. Treatment of HUVECs with monoclonal antibody for LOX-1 attenuated RLP-mediated production of superoxide, TNF-α, and interleukin-1β and DNA fragmentation.
Conclusions—
RLPs stimulated NAD(P)H oxidase–dependent superoxide formation and induction of cytokines in HUVECs via activation of LOX-1, consequently leading to reduction in cell viability with DNA fragmentation, and cilostazol exerts a cell-protective effect by suppressing these variables.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
231 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Cumulative remnant cholesterol exposure during young adulthood and middle age and risk of cardiovascular events: A 30-year population-based cohort study;International Journal of Cardiology;2024-11
2. Association between remnant cholesterol and the risk of cardiovascular disease in Chinese population;Journal of Stroke and Cerebrovascular Diseases;2024-08
3. Association of remnant cholesterol with renal function and its progression in patients with type 2 diabetes related chronic kidney disease;Frontiers in Endocrinology;2024-07-04
4. Triglyceride-rich lipoprotein, remnant cholesterol, and apolipoproteins CII, CIII, and E in patients with schizophrenia;Journal of Lipid Research;2024-07
5. Cilostazol protects against gastric ulcers by regulating PPAR-γ, HO-1, PECAM-1, pErk-1, NF-κB, Bcl-2, and cleaved caspase-3 protein expression;Naunyn-Schmiedeberg's Archives of Pharmacology;2024-06-17