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Cellular and molecular mechanisms of endothelial cell dysfunction.

1997/11/01 by D G Harrison, David G. Harrison · 1,053 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Amino acid #Antithrombotic #Arginine #Biochemistry #Biology #Cell #Cell function #Eicosanoids and Hypertension Pharmacology #Endothelial dysfunction #Endothelial stem cell #Endothelium #In vitro #Inflammation #Internal medicine #Medicine #Nitric Oxide and Endothelin Effects #Nitric oxide #Nitric oxide synthase #Pathophysiology #Renin-Angiotensin System Studies #Vascular tone

paper · pdf · doi:10.1172/jci119751

published in Journal of Clinical Investigation 100(9), 2153-2157 (American Society for Clinical Investigation)

openalex publication_date 1997/11/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27

Abstract

repeated observation that it is altered by a variety of pathophysiological conditions. Such alterations of NO production and/or bioavailability have been shown to occur both in experimental animal models and in human subjects, in the setting of such diverse disorders as hypertension, hypercholesterolemia, aging, cigarette smoking, diabetes, and heart failure (1). The mechanisms underlying the alteration of this important function of the endothelium are varied and likely multifactorial. During the past several years an enormous amount of research has been devoted to understanding these abnormalities, which has led to new insights into regulation of vascular tone, redox state, inflammation, growth, and the prothrombotic/antithrombotic properties of the vessel wall. This Perspective will highlight some of these important new observations, as they relate to the pathology of the endothelial cell L -arginine/NO synthase (NOS) system. In addition, future directions of research that may be particularly informative will be indicated. Alterations of the substrate for the NOS enzyme The substrate for NOS is the basic amino acid L -arginine (with a K m of approximately 5 m M, reference 2). L -Arginine is syn

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