An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation

Abstract

Microsomes prepared from rabbit or pig aortas transformed endoperoxides (PGG2 or PGH2) to an unstable substance (PGX) that inhibited human platelet aggregation. PGX was 30 times more potent in this respect than prostaglandin E1. PGX contracted some gastrointestinal smooth muscle and relaxed certain isolated blood vessels. Prostaglandin endoperoxides cause platelet aggregation possibly through the generation by platelets of thromboxane A2. Generation of PGX by vessel walls could be the biochemical mechanism underlying their unique ability to resist platelet adhesion. A balance between formation of anti- and pro-aggregatory substances by enzymes could also contribute to the maintenance of the integrity of vascular endothelium and explain the mechanism of formation of intra-arterial thrombi in certain physiopathological conditions.

Integrated Regional Cardiac Hemodynamic Imaging and RNA Sequencing Reveal Corresponding Heterogeneity of Ventricular Wall Shear Stress and Endocardial Transcriptome

“…Furthermore, RNAseq identified differential expression of prostacyclin synthase (PTGIS) in the apex. Prostacyclin synthase, the primary enzyme responsible for production of prostacyclin, an integral inhibitor of platelet activation,24 was 5‐fold higher in the LV apex than base EECs (Figure 8B).…”

Pulmonary vascular changes in asthma and COPD

“…However, additional preclinical and clinical studies with patients with different disease stages of COPD are warranted to address this hypothesis. Prostacyclin is in homeostatic balance with thromboxane in the circulatory system [113,114], where thromboxane is mainly produced by thrombocytes via the COX pathway and known as a potent vaso-and bronchoconstrictor in both human and animals [115,116]. Patients with COPD have an increased amount of thromboxane metabolites in their urine [117], probably due to hypoxia and increased platelet aggregation, which correlates with the augmented amount of plaque in the vessels of these patients [118].…”

Endothelial cell functions

“…Endothelium generates PGI 2 , which relaxes the underlying smooth muscle cells through activation of adenylate cyclase and subsequent generation of cAMP. Endothelial cells constitutively release PGI 2 (Moncada et al, 1976) which appears to be involved in the regulation of resting vascular tone, in addition to EDRF. It is released in higher amount in response to ligand binding on the cell surface such as thrombin, arachidonic acid, histamine, serotonin, .…”