{'fraction_non_alphanumeric': 0.025838926174496644, 'fraction_numerical': 0.013422818791946308, 'mean_word_length': 5.210416666666666, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Lipocalin-type PGD synthase as a novel biomarker for coronary vasospasm.

oronary artery spasm is defined as abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia. Coronary artery spasm plays an important role in the pathogenesis of not only variant angina1,2 but the other forms of ischemic heart disease such as myocardial infarction.3 Considering the fact that esophageal motility is enhanced in patients with angina pectoris due to coronary spasm (ie, vasospastic angina (VSA)),4 the presence of a generalized disorder of smooth muscle contraction is strongly suggested. To date, the clinical features of VSA have been well characterized, and the treatment almost established. However, the underlying mechanisms for coronary spasm are not fully determined, and useful biomarkers also have not been identified. Endothelial dysfunction through abnormalities of nitric oxide (NO) synthase and its reduced bioavailability, and hypercontractility of vascular smooth muscle in spastic arteries, are factors in the development of VSA. Mutations (Glu298Asp variation in exon 7 and T-786 C in the 5’ flanking region) of the endothelial NO synthase gene have been shown to be associated with coronary spasm.5,6 In other reports, NO is not necessarily decreased at the sites of spasticity of the coronary arteries, suggesting additional mechanisms inducing focal smooth muscle cell hypersensitivity in patients with variant angina. We recently showed the pivotal role of phospholipase C (PLC)-δ1 in the genesis of VSA in humans. PLC-δ1 is an isoform of PLC that is more sensitive to Ca2+ than the other isozymes; therefore, the initial increase in Ca2+ induced by G protein-linked PLC induces the prolonged activation of PLC-δ1 via positive feedback. PLC-δ1 activity was 3-fold higher in the cultured skin fibroblasts obtained from VSA patients than that from control subjects,7 and its activity positively correlated with coronary artery vasomotility. A single base variant (864G-A) in the entire coding region of the PLC-δ1 gene, resulting in the amino acid replacement of arginine 257 by histidine and enhanced activity,8 was found in 10% of the VSA patients, whereas p122 protein, which was recently cloned to potentiate PLC-δ1 activity, was increased 3-fold in patients with VSA compared with control subjects.9 Another enzyme related to constriction, ROCK/Rho kinase, was also reported to play an important role in the genesis of VSA. The porcine models of coronary artery spasm were developed by chronic application of interleukin-β to the coronary artery and by removal of the endothelium with high-cholesterol feeding. Increased expression of ROCK/Rho kinase messenger RNA was demonstrated at the spastic segment compared with the control in the porcine model. In patients with VSA, the Rho-kinase inhibitor, fasudil, attenuated the constrictor response of the coronary artery to acetylcholine (ACh) and prevented the occurrence of chest pain.10