Showing posts with label Endothelium. Show all posts
Showing posts with label Endothelium. Show all posts

Sunday, 22 June 2025

Exploring the Biomedical Significance of Oxidized Phospholipids as Biomarkers, Drug Targets and Drug Leads Across Multiple Diseases | Chapter 11 | Pharmaceutical Research: Recent Advances and Trends Vol. 6

Enzymatic oxidation or autooxidation of esterified polyunsaturated fatty acids (PUFA) residues within phospholipids in cell membranes or circulating lipoprotein particles leads to the formation of a broad range of oxidized phospholipid (OxPL) species. During the last two decades, OxPLs have been extensively characterized as drivers of pathology in multiple inflammatory and metabolic conditions. Chronically elevated OxPL levels present in tissues, circulation, and atherosclerotic plaques are thought to induce or accompany pro-inflammatory and injurious effects on blood-, vessel wall cells as well as cells in different organs, which can lead to the development or worsening of metabolic, cardiovascular diseases, age-associated brain diseases, allergy, asthma, cancer or inflammatory pain. Analysis of the structure-activity relationship however identified specific OxPL products exhibiting prominent anti-inflammatory, pro-survival, and endothelial barrier protective properties. This study reviewed and briefly summarized the rapidly accumulating evidence pointing to the importance of OxPLs in pathology where they can play multiple roles of biomarkers, drug targets, and drug leads.

 

Author (s) Details

Olga V. Oskolkova
Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Humboldtstrasse 46/III, 8010 Graz, Austria.

 

Anna A. Birukova
Department of Anesthesiology, University of Maryland School of Medicine, 20 Penn. Street, HSF-2, Room 145, Baltimore, MD 21201, USA.

Konstantin G. Birukov
Department of Anesthesiology, University of Maryland School of Medicine, 20 Penn. Street, HSF-2, Room 145, Baltimore, MD 21201, USA.

 

Valery N. Bochkov
Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, University of Graz, Humboldtstrasse 46/III, 8010 Graz, Austria and Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria.

 

Please see the book here:- https://doi.org/10.9734/bpi/prrat/v6/1771

Monday, 20 September 2021

Coronary Luminal Endothelial Lectinic Proteins upon Binding to N-Acetylglucosamine Become the Sensors to Flow That Induce Cardiac Paracrine-Dependent Responses | Chapter 8 | New Visions in Biological Science Vol. 3

When coronary blood flow is applied to the endothelium lumen, paracrine effectors change parenchymal processes, however the mechanism of flow sensation is unknown. We and others have established that oligosaccharides and lectins in the coronary endothelial luminal membrane (CELM) are involved in flow detection, and we postulated that a reversible flow-modulated lectin-oligosaccharide interaction causes cardiac effects of coronary flow. Lectins are a family of proteins found throughout nature that have a strong affinity for specific oligosaccharide sequences, allowing them to recognise specific molecules. It has recently been proposed that glycosylated and amiloride-sensitive Na+/Ca++ channels (ENaCs) play a role in flow-induced endothelial responses. The purpose of this study is to isolate and characterise CELM GlcNac-binding lectins and establish their function in cardiac and vascular flow-induced effects because N-acetylglucosamine (GlcNac) is a significant component of glycocalyx oligosaccharides (i.e., hyaluronan (-4GlcUA1-3GlcNAc1-]n). For this, we developed a 460-kDa GlcNac polymer (GlcNac-Pol) with high affinity for GlcNac-recognizing lectins. GlcNac-Pol, which binds to CELM, is treated intracoronally to diminish flow-dependent positive inotropic and dromotropic effects in the heart. CELM was isolated using GlcNac-Pol as an affinity probe. There were at least 35 lectinic peptides produced by GlcNac-Pol-recognizing lectins, one of which was the -ENaC channel. GlcNac-Pol-induced activities and flow sensing may be mediated by some of these lectins. A flow-responsive and well-accepted model of endothelial-parenchymal paracrine interaction was also used, in which isolated blood arteries were perfused at constant flow rates. We discovered that GlcNac-Pol, nitro-L-arginine methyl ester, indomethacin, amiloride, and hyaluronidase attached to the endothelium luminal membrane (ELM) inhibit flow-induced vasodilation (FIV). The effect of hyaluronidase was reversed by infusing soluble hyaluronan. GlcNac-Pol inhibits FIV by competing with intrinsic hyaluronan attached to a lectinic structure, such as the amiloride-sensitive ENaC, and displacing it, according to these findings. Nitric oxide and prostaglandins are thought to be FIV's paracrine mediators.


Author (S) Details


Juan Ramiro-Diaz

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico.


Alma Barajas-Espinosa

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico.


Erika Chi-Ahumada

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico.


Sandra Perez-Aguilar

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico.


David Torres-Tirado

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico.


Jesus Castillo-Hernandez

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico


Maureen Knabb

Biology, West Chester University, West Chester, Pennsylvania, USA.


Ana Barba de la Rosa

Departamento de Biologia Molecular, Instituto Potosino de Investigacion Cientifica y Tecnologica, San Luis Potosi, Mexico.


Rafael Rubio

Departamento de Fisiologia, Universidad Autonoma de San Luis Potosi, Mexico.


View Book :- https://stm.bookpi.org/NVBS-V3/article/view/3937