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Circulating microparticles released during dyslipidemia may exert deleterious effects on blood vessels and endothelial function
Affiliation:1. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia;2. Department of Cell Signaling, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992 Russia;3. Department of Neurosciences, Biochemistry Group, University of Oldenburg, Oldenburg, 26111 Germany;4. Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia;5. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia;6. Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow 119991, Russia;1. School of Biology, Georgia Institute of Technology, 310 Ferst Drive NW, Atlanta, GA 30332, USA;2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive NW, Atlanta, GA 30332, USA;3. Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA 23284, USA;1. Department of Biology, Shahed University, Tehran, Iran;2. Department of Biology, Faculty of Science, Imam Hussein University, Tehran, Iran;1. School of Biology, Georgia Institute of Technology, 310 Ferst Dr. NW, Atlanta, GA, USA;2. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA;3. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;4. School of Engineering, Virginia Commonwealth University, 601 West Main Street, Richmond, VA, USA;5. Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;1. College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Republic of Korea;2. College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea;3. College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea;4. Department of Periodontics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
Abstract:AimsTo compare the bioactivity of circulating microparticles (MPs) isolated from dyslipidemic Psammomys obesus (P. obesus) fed a high-energy diet (HED) with those released from healthy P. obesus fed a normal diet (ND).MethodsVascular reactivity of aortic rings was evaluated by myography, after 24 h incubation in the absence or in the presence of circulating MPs isolated, by differential centrifugations, from the plasma of animals subjected to HED (MPsHED) or ND (MPsND) for 12 weeks. Human umbilical vein endothelial cells (HUVECs) were treated for 24 h with MPsHED or MPsND animals and subjected to immunofluorescence staining of caveolin-1 (cav-1), intercellular adhesion molecule-1 (ICAM-1), endothelial nitric oxide synthase (eNOS), F-actin and reactive oxygen species (ROS) detection.ResultsThe HED exerted a distinctly pronounced hyperlipidemic effect marked by plasmatic increase of total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride (TG). Both MPsND and MPsHED induced a significant reduction of maximal relaxation induced by acetylcholine (ACh). Interestingly, MPsHED significantly decreased eNOS expression up to ~25% and increased ROS production up to ~75% on in vitro treated HUVECs. Moreover, in HUVECs, MPsHED significantly decreased cav-1 expression up to ~50% whereas significant increase of ICAM-1 expression by about 2-fold approximately was observed.ConclusionOur experimental study demonstrated the dual role of MPs on vascular function by modulating endothelial cell function. Furthermore, MPs may be considered as vectors of a bioactive information contributing to inflammation and vascular damage.
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