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Evidence for involvement of calcitonin gene-related peptide in nitroglycerin response and association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism.
J Am Coll Cardiol. 2008 Sep 09; 52(11):953-60.JACC

Abstract

OBJECTIVES

This study sought to determine whether calcitonin gene-related peptide (CGRP) is involved in glyceryl trinitrate (GTN) response in humans, and its association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism.

BACKGROUND

In animal models, CGRP contributes to the cardiovascular effects of GTN. The enzyme principally responsible for GTN bioactivation is ALDH2. The common ALDH2*2 polymorphism is associated with a lack of GTN efficacy.

METHODS

In 18 ALDH2*2-genotyped Chinese volunteers, we observed the changes in plasma concentrations of CGRP after sublingual GTN administration and its correlation with GTN response, and assessed the expression of CGRP messenger ribonucleic acid (mRNA) in cultured peripheral blood mononuclear cells (PBMCs) pre-treated with 10(-5) mol/l GTN.

RESULTS

In contrast to carriers of the ALDH2*2 allele, ALDH2*1/*1 homozygotes showed a significantly higher extent of absolute changes in both systolic blood pressure (DeltaSBP) and HR (DeltaHR) at several time points after GTN administration. Plasma concentrations of CGRP were increased significantly 12 min after GTN administration, the percentage increase in plasma concentrations of CGRP correlated positively with both DeltaSBP and DeltaHR, and percentage increase in plasma concentrations of CGRP was significantly higher in ALDH2*1/*1 homozygotes. In addition, PBMCs from ALDH2*1/*1 homozygotes showed a higher-fold increase in both CGRP I and CGRP II mRNA after GTN stimulation, and the GTN-induced increase in CGRP mRNA expression in PBMCs from ALDH2*1/*1 homozygotes was inhibited by the ALDH2 inhibitor chloral hydrate.

CONCLUSIONS

We found that CGRP is associated with the cardiovascular effect of GTN through an ALDH2-dependent pathway in humans.

Authors+Show Affiliations

Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, Hunan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18772068

Citation

Guo, Ren, et al. "Evidence for Involvement of Calcitonin Gene-related Peptide in Nitroglycerin Response and Association With Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism." Journal of the American College of Cardiology, vol. 52, no. 11, 2008, pp. 953-60.
Guo R, Chen XP, Guo X, et al. Evidence for involvement of calcitonin gene-related peptide in nitroglycerin response and association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism. J Am Coll Cardiol. 2008;52(11):953-60.
Guo, R., Chen, X. P., Guo, X., Chen, L., Li, D., Peng, J., & Li, Y. J. (2008). Evidence for involvement of calcitonin gene-related peptide in nitroglycerin response and association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism. Journal of the American College of Cardiology, 52(11), 953-60. https://doi.org/10.1016/j.jacc.2008.05.049
Guo R, et al. Evidence for Involvement of Calcitonin Gene-related Peptide in Nitroglycerin Response and Association With Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism. J Am Coll Cardiol. 2008 Sep 9;52(11):953-60. PubMed PMID: 18772068.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for involvement of calcitonin gene-related peptide in nitroglycerin response and association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism. AU - Guo,Ren, AU - Chen,Xiao-Ping, AU - Guo,Xin, AU - Chen,Lei, AU - Li,Dai, AU - Peng,Jun, AU - Li,Yuan-Jian, PY - 2008/02/01/received PY - 2008/04/28/revised PY - 2008/05/19/accepted PY - 2008/9/6/pubmed PY - 2008/10/3/medline PY - 2008/9/6/entrez SP - 953 EP - 60 JF - Journal of the American College of Cardiology JO - J Am Coll Cardiol VL - 52 IS - 11 N2 - OBJECTIVES: This study sought to determine whether calcitonin gene-related peptide (CGRP) is involved in glyceryl trinitrate (GTN) response in humans, and its association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism. BACKGROUND: In animal models, CGRP contributes to the cardiovascular effects of GTN. The enzyme principally responsible for GTN bioactivation is ALDH2. The common ALDH2*2 polymorphism is associated with a lack of GTN efficacy. METHODS: In 18 ALDH2*2-genotyped Chinese volunteers, we observed the changes in plasma concentrations of CGRP after sublingual GTN administration and its correlation with GTN response, and assessed the expression of CGRP messenger ribonucleic acid (mRNA) in cultured peripheral blood mononuclear cells (PBMCs) pre-treated with 10(-5) mol/l GTN. RESULTS: In contrast to carriers of the ALDH2*2 allele, ALDH2*1/*1 homozygotes showed a significantly higher extent of absolute changes in both systolic blood pressure (DeltaSBP) and HR (DeltaHR) at several time points after GTN administration. Plasma concentrations of CGRP were increased significantly 12 min after GTN administration, the percentage increase in plasma concentrations of CGRP correlated positively with both DeltaSBP and DeltaHR, and percentage increase in plasma concentrations of CGRP was significantly higher in ALDH2*1/*1 homozygotes. In addition, PBMCs from ALDH2*1/*1 homozygotes showed a higher-fold increase in both CGRP I and CGRP II mRNA after GTN stimulation, and the GTN-induced increase in CGRP mRNA expression in PBMCs from ALDH2*1/*1 homozygotes was inhibited by the ALDH2 inhibitor chloral hydrate. CONCLUSIONS: We found that CGRP is associated with the cardiovascular effect of GTN through an ALDH2-dependent pathway in humans. SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/18772068/Evidence_for_involvement_of_calcitonin_gene_related_peptide_in_nitroglycerin_response_and_association_with_mitochondrial_aldehyde_dehydrogenase_2__ALDH2__Glu504Lys_polymorphism_ DB - PRIME DP - Unbound Medicine ER -