title: Alterations in plasma membrane promote overexpression and increase of sodium influx through epithelial sodium channel in hypertensive platelets.
abstract: Platelets are small, anucleated cell fragments that activate in response to a wide variety of stimuli, triggering a complex series of intracellular pathways leading to a hemostatic thrombus formation at vascular injury sites. However, in essential hypertension, platelet activation contributes to causing myocardial infarction and ischemic stroke. Reported abnormalities in platelet functions, such as platelet hyperactivity and hyperaggregability to several agonists, contribute to the pathogenesis and complications of thrombotic events associated with hypertension. Platelet membrane lipid composition and fluidity are determining for protein site accessibility, structural arrangement of platelet surface, and response to appropriate stimuli. The present study aimed to demonstrate whether structural and biochemical abnormalities in lipid membrane composition and fluidity characteristic of platelets from hypertensive patients influence the expression of the Epithelial Sodium Channel (ENaC), fundamental for sodium influx during collagen activation. Wb, cytometry and quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) assays demonstrated ENaC overexpression in platelets from hypertensive subjects and in relation to control subjects. Additionally, our results strongly suggest a key role of β-dystroglycan as a scaffold for the organization of ENaC and associated proteins. Understanding of the mechanisms of platelet alterations in hypertension should provide valuable information for the pathophysiology of hypertension.
authors.affiliation: Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), México City, México. Electronic address: dcereced@prodigy.net.mx.
authors.forename: D
authors.initials: D
authors.lastname: Cerecedo
authors.affiliation: Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía (ENMH), Instituto Politécnico Nacional (IPN), México City, México.
authors.forename: Ivette
authors.initials: I
authors.lastname: Martínez-Vieyra
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), P.O. Box 70-159, 04510, D.F., México City, México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosa-Peinado
authors.affiliation: Laboratorio de Biología Celular y Productos Naturales, ENMH, IPN, México City, México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cornejo-Garrido
authors.affiliation: Laboratorio de Biología Celular y Productos Naturales, ENMH, IPN, México City, México.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ordaz-Pichardo
authors.affiliation: Laboratorio de Bioquímica, ENMH, IPN, México City, México.
authors.forename: Claudia
authors.initials: C
authors.lastname: Benítez-Cardoza
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000494:pharmacology; D022461:Caveolins / Q000097:blood; D049030:Dystroglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D053503:Epithelial Sodium Channels / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood*; D017136:Ion Transport; D008297:Male; D008560:Membrane Fluidity; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012964:Sodium / Q000097:blood*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; C483081:DAG1 protein, human; D053503:Epithelial Sodium Channels; D034741:RNA, Small Interfering; C507045:SCNN1A protein, human; D049030:Dystroglycans; D000450:Aldosterone; D012964:Sodium; D006854:Hydrocortisone
keywords: Caveolin-1; Dystroglycan; ENaC overexpression; HPLC; Hypertensive platelets; Membrane fluidity