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Alterations to plasma membrane lipid contents affect the biophysical properties of erythrocytes from individuals with hypertension
Authors:!vette Martínez-Vieyra  Mario Rodríguez-Varela  Diana García-Rubio  Beatriz De la Mora-Mojica  Juan Méndez-Méndez  Carlos Durán-Álvarez  Doris Cerecedo
Affiliation:1. Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, CDMX, Mexico;2. Instituto de Ciencias Aplicadas y Tecnología, Universidad Nacional Autónoma de México, CDMX, Mexico;3. CONACyT Fellow-ICAT, Universidad Nacional Autónoma de México, CDMX, México;4. Centro de Nanociencias y Micro y Nanotecnología, I.P.N., CDMX, México
Abstract:Genetic and environmental factors may contribute to high blood pressure, which is termed essential hypertension. Hypertension is a major independent risk factor for cardiovascular disease, stroke and renal failure; thus, elucidation of the etiopathology of hypertension merits further research. We recently reported that the platelets and neutrophils of patients with hypertension exhibit altered biophysical characteristics. In the present study, we assessed whether the major structural elements of erythrocyte plasma membranes are altered in individuals with hypertension. We compared the phospholipid (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingosine) and cholesterol contents of erythrocytes from individuals with hypertension (HTN) and healthy individuals (HI) using LC/MS-MS. HTN erythrocytes contained higher phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine contents and a lower cholesterol content than HI erythrocytes. Furthermore, atomic force microscopy revealed important morphological changes in HTN erythrocytes, which reflected the increased membrane fragility and fluidity and higher levels of oxidative stress observed in HTN erythrocytes using spectrophotofluorometry, flow cytometry and spectrometry. This study reveals that alterations to the lipid contents of erythrocyte plasma membranes occur in hypertension, and these alterations in lipid composition result in morphological and physiological abnormalities that modify the dynamic properties of erythrocytes and contribute to the pathophysiology of hypertension.
Keywords:Corresponding author at: Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, I.P.N., Guillermo Massieu Helguera No. 239, Col. La Escalera Ticomán, 07320 (CDMX), Mexico.  AFM  atomic force microscopy  ANOVA  Analysis of Variance  BW  body weight  CH  cholesterol  DCF  2′,7′-dichlorofluorescein diacetate  FACS  Fluorescence-Activated Cell Sorting  FBS  fetal bovine serum  GSH  glutathione  HPLC  high performance liquid chromatography  HI  healthy individuals  HTN  hypertension  LC-MS/MS  liquid chromatography coupled to mass spectrometry with triple quadrupole  Lo  liquid-ordered  LORCA  laser-assisted optical rotational red cell analyzer  PBS  phosphate buffer saline  PC  phosphatidylcholine  PE  phosphatidylethanolamine  PS  phosphatidylserine  PSMF  phenylmethanesulfonyl fluoride  ROS  reactive oxygen species  SM  sphingomyelin  S1P  sphingosine phosphate  TMA-DPH  1-(4-TriMethylAmmoniumphenyl)-6-Phenyl-1, 3, 5-Hexatriene  Liquid chromatography  Tandem mass spectrometry  Red blood cells  Membrane fluidity  Oxidative stress  Hemolysis
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