Title of article :
Evidence for Involvement of Calcitonin Gene-Related Peptide in Nitroglycerin Response and Association With Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism
Author/Authors :
Ren Guo، نويسنده , , Xiao-Ping Chen، نويسنده , , Xin Guo، نويسنده , , Lei Chen، نويسنده , , Dai Li، نويسنده , , Jun Peng، نويسنده , , Yuan-Jian Li، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Pages :
8
From page :
953
To page :
960
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 (ΔSBP) and HR (ΔHR) 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 ΔSBP and ΔHR, 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.
Keywords :
peripheral blood mononuclear cells , genetic polymorphism , Nitroglycerin , calcitonin gene-related peptide , mitochondrial aldehyde dehydrogenase-2
Journal title :
JACC (Journal of the American College of Cardiology)
Serial Year :
2008
Journal title :
JACC (Journal of the American College of Cardiology)
Record number :
473565
Link To Document :
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