Cardiac levels of NOS1AP RNA from right ventricular tissue recovered during lead extraction.
BACKGROUND
There is a scarcity of cardiac tissue available for research.


OBJECTIVE
(1) To investigate the feasibility of obtaining myocardial tissue from extracted pacemaker and defibrillator leads for gene expression analysis and (2) to examine the nitric oxide 1 adaptor protein (NOS1AP) RNA expression as a function of patient genotype.


METHODS
Seventeen patients (age = 56 ± 20 years; 12 men; 5 pacemakers; 12 defibrillators) undergoing lead extractions for standard indications (5 device erosion; 1 vascular occlusion; 11 lead malfunction or recall) were genotyped for 2 NOS1AP single nucleotide polymorphisms-rs10494366 (T to G) and rs10918594 (C to G)-and had RNA levels measured by real-time polymerase chain reaction for collagen I, troponin I, Ca(v)1.2, Kv4.3, HERG, KvLQT1, connexin 43, NOS1AP, and sodium-calcium exchanger. Ventricular tissue obtained from 3 failing hearts at transplantation served as reference.


RESULTS
A high ratio of cardiac troponin I/collagen I RNA identified 9 of the 17 patient samples (muscle rich), in which the gene expression profile was similar to that of the reference ventricular samples and significantly different (P < .003) from the expression profile of samples with a low troponin I/collagen ratio (muscle poor). TT and CC polymorphisms were associated with significantly lower NOS1AP RNA levels (P < .01 compared with the GG genotype).


CONCLUSIONS
Performing gene expression analyses on right ventricular tissue samples extracted with pacemaker and defibrillator leads is feasible. A significant number of samples contain cardiomyocytes that express troponin I and ion channels at levels comparable to those seen in explanted hearts. Decreased NOS1AP expression in rs10494366 TT and rs10918594 CC homozygotes may underlie shorter repolarization times.
Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. sabas@upmc.edu
Samir
S
Saba
Haider
H
Mehdi
Hemal
H
Shah
Zahid
Z
Islam
Elie
E
Aoun
Sammy
S
Termanini
Reem
R
Mahjoub
Ryan
R
Aleong
Charles F
CF
McTiernan
Barry
B
London
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D002304:Cardiac Pacing, Artificial / Q000379:methods; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D005240:Feasibility Studies; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods*; D055106:Genome-Wide Association Study; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016027:Heart Transplantation / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000473:pathology*; D010138:Pacemaker, Artificial; D020641:Polymorphism, Single Nucleotide; D019831:Sodium-Calcium Exchanger / Q000235:genetics; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; C488081:NOS1AP protein, human; D019831:Sodium-Calcium Exchanger