This Article Full Text Full Text (PDF) All Versions of this Article: 105/17/2024    most recent 01.CIR.0000014613.36469.3Fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakano, T. Articles by Okumura, K. Search for Related Content PubMed PubMed Citation Articles by Nakano, T. Articles by Okumura, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Related Collections Chronic ischemic heart disease

(Circulation. 2002;105:2024.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Enhanced Activity of Variant Phospholipase C-1 Protein (R257H) Detected in Patients With Coronary Artery Spasm

Takao Nakano, MD; Tomohiro Osanai, MD; Hirofumi Tomita, MD; Masayuki Sekimata, PhD; Yoshimi Homma, PhD; Ken Okumura, MD

From the Second Department of Internal Medicine (T.N., T.O., H.T., K.O.), Hirosaki University School of Medicine, Hirosaki, and Department of Biomolecular Science (M.S., Y.H.), Fukushima Medical University School of Medicine, Fukushima, Japan.

Correspondence to Ken Okumura, MD, The Second Department of Internal Medicine, Hirosaki University School of Medicine, Zaifu-cho 5, Hirosaki, 036-8562 Japan. E-mail okumura{at}cc.hirosaki-u.ac.jp

Background— We recently demonstrated that phospholipase C (PLC)–1 activity in cultured skin fibroblasts obtained from patients with coronary spastic angina (CSA) is enhanced. We tested the hypothesis that structural abnormality in PLC-1 isoform is a cause of the enhanced activity.

Methods and Results— Sequence analysis of the cDNA coding for PLC-1 obtained from fibroblasts revealed that one conversion of guanine to adenine (A) was present at nucleotide position 864 in one CSA patient, resulting in the amino acid replacement of arginine 257 by histidine (R257H). The incidence of 864A/A in genomic DNA, analyzed by single-strand conformation polymorphism, was greater in patients with CSA than in male control subjects (6 of 57 patients with CSA versus 1 of 62 control subjects, P<0.05). The activity of the variant PLC-1 protein under free calcium concentration between 10^-8 and 10^-7 mol/L was 2-fold higher than that of the wild-type protein. Baseline intracellular calcium concentration ([Ca²⁺]_i) in human embryonic kidney 293 cells transfected with the variant PLC-1 was higher than that in cells with the wild type. The peak increase in [Ca²⁺]_i in response to acetylcholine at 10^-6 and 10^-5 mol/L was greater in the cells with the variant PLC-1 than in those with the wild type.

Conclusions— These findings indicate that the R257H variant in the PLC-1 gene detected in patients with CSA is associated with enhancement of enzyme activity, and they describe a novel mechanism for the enhanced coronary vasomotility in CSA.

Key Words: vasospasm • muscle, smooth • calcium • acetylcholine

This article has been cited by other articles:

				S. Stern and A. Bayes de Luna Coronary Artery Spasm: A 2009 Update Circulation, May 12, 2009; 119(18): 2531 - 2534. [Full Text] [PDF]