Alterations in plasma membrane promote overexpression and increase of sodium influx through epithelial sodium channel in hypertensive platelets

• Published in: Biochimica et biophysica acta 2016-08, Vol.1858 (8), p.1891-1903
• Main Authors: Cerecedo, D., Martínez-Vieyra, Ivette, Sosa-Peinado, Alejandro, Cornejo-Garrido, Jorge, Ordaz-Pichardo, Cynthia, Benítez-Cardoza, Claudia
• Format: Article
• Language: English
• Subjects: Aged; Aldosterone - blood; Blood Platelets - metabolism; Blood Platelets - ultrastructure; Case-Control Studies; Caveolin 1 - pharmacology; Caveolin-1; Caveolins - blood; Dystroglycan; Dystroglycans - antagonists & inhibitors; Dystroglycans - biosynthesis; Dystroglycans - blood; Dystroglycans - genetics; ENaC overexpression; Epithelial Sodium Channels - biosynthesis; Epithelial Sodium Channels - blood; Epithelial Sodium Channels - genetics; Female; Gene Expression Regulation - drug effects; HPLC; Humans; Hydrocortisone - blood; Hypertension - blood; Hypertensive platelets; Ion Transport; Male; Membrane Fluidity; Middle Aged; RNA Interference; RNA, Small Interfering - genetics; Sodium - blood
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2016.04.015

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. [Display omitted] •Epithelial Sodium Channel is overexpressed in platelets from hypertensive patients.•Cholesterol and Phosphatidilcholine are down expressed in platelet membranes from hypertensive patients.•Caveolin-1 is overexpressed in platelets from hypertensive patients.•Beta-dystroglycan is a structural scaffold for Epithelial Sodium Channel.