Background: Thromboxane A synthase (TXAS) metabolizes the cyclooxygenase product prostaglandin (PG) H2 into thromboxane H2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation. Nonsynonymous polymorphisms in the TXAS gene have the potential to alter TXAS activity and affect TXA2 generation.
Objectives: The aim of this study was to assess the functional effects of genetic variants in the TXAS protein, including K258E, L357V, Q417E, E450K, and T451N.
Methods: Wild-type TXAS and the variant proteins were expressed in a bacterial system and purified by affinity and hydroxyapatite chromatography. The two characteristic catalytic activities of TXAS were assayed in each of the purified recombinant proteins: isomerization of PGH2 to TXA2 and fragmentation of PGH2 to 12-hydroxyheptadecatrienoic acid and malondialdehyde.
Results: All of the variants showed both isomerization and fragmentation activities. The Km values of the variants ranged from 27 to 52 µmol/l PGH2 (wild-type value: 32 μmol/l PGH2); the Vmax values of the variants ranged from 18 to 40 U/mg (wild-type value: 41 U/mg). The kinetic differences were largest for the L357V variant, whose Vmax/Km ratio was just 27% of the wild-type value.
Conclusion: The increased Km and decreased Vmax values observed with L357V suggest that this variant may generate less TXA2 at the low levels of PGH2 expected in vivo, raising the possibility of attenuated signaling through the thromboxane pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434599 | PMC |
| http://dx.doi.org/10.1097/FPC.0b013e3283562d82 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Endothelial Cell-Selective Adhesion Molecule Deficiency Exhibit Increased Pulmonary Vascular Resistance Due to Impaired Endothelial Nitric Oxide Signaling.
Am J Physiol Heart Circ Physiol
December 2024
Department of Physiology.
Endothelial cell-selective adhesion molecule (ESAM) is a member of tight junction molecules, highly abundant in the heart and the lung, and plays a role in regulating endothelial cell permeability. We previously reported that mice with genetic ESAM deficiency (ESAM) exhibit coronary microvascular dysfunction leading to the development of left ventricular diastolic dysfunction. Here, we hypothesize that ESAM mice display impairments in the pulmonary vasculature, affecting the overall pulmonary vascular resistance (PVR).
View Article and Find Full Text PDF[Serum metabolomics reveals effects of standard decoction and formula granules of Paeoniae Radix Rubra on rat model of heat toxin and blood stasis].
Zhongguo Zhong Yao Za Zhi
October 2024
Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine Guangzhou 510095, China Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Research and Development Guangzhou 510095, China.
This study aims to compare the effects and mechanisms of the standard decoction and formula granules of Paeoniae Radix Rubra in regulating the metabolism in the rat model of heat toxin and blood stasis. SD rats were randomized into control, model, standard decoction, and formula granules groups. After 14 days of administration, the rats in the latter three groups were subjected to subcutaneous injection with carrageenan and intraperitoneal injection with bacterial lipopolysaccharide for the modeling of heat toxin and blood stasis.
View Article and Find Full Text PDFRole of plasma neuropeptide Y in acute myocardial infarction: a case-control study.
BMC Cardiovasc Disord
November 2024
Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Background: As neuropeptide Y is associated with endothelial dysfunction, this study explored the relationship between neuropeptide Y and acute myocardial infarction.
Methods: We included 128 acute myocardial infarction cases and 62 controls. Using the SYNTAX scoring system, the acute myocardial infarction group was sub-grouped into "SYNTAX ≤ 22," "SYNTAX = 23-32," and "SYNTAX ≥ 33.
In vitro evidence that the vasorelaxant effects of 2-nitro-1-phenyl-1-propanol on rat coronary arteries involve cyclic nucleotide pathways.
Fundam Clin Pharmacol
February 2025
Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
The synthetic nitro-alcohol 2-nitro-1-phenyl-1-propanol (NPP) has endothelium-independent relaxing properties in isolated preparations of rat aorta and mesenteric artery. In this study, we investigated whether the vasodilator effects occur in coronary vessels and explored whether hyperpolarization is involved in the underlying mechanism of NPP-induced smooth muscle relaxation. The relaxing responses were studied in isolated preparations of the left anterior descending coronary (ADC) and the septal coronary (SC) arteries, which had been previously maintained under sustained contraction induced by the thromboxane A analogue U-46619.
View Article and Find Full Text PDFRole of L-type Ca-channels in the vasorelaxing response to finerenone in arteries of human visceral adipose tissue.
Physiol Rep
September 2024
Department of Systems Medicine, Tor Vergata University, Rome, Italy.
Inadequate blood supply to the expanding adipose tissue (AT) is involved in the unhealthy AT remodeling and cardiometabolic consequences of obesity. Because of the pathophysiological role of upregulated mineralocorticoid receptor (MR) signaling in the complications of obesity, this study tested the vasoactive properties of finerenone, a nonsteroidal MR antagonist, in arteries of human AT. Arteries isolated from the visceral AT of obese subjects were studied in a wire myograph.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!