Cardiac levels of NOS1AP RNA from right ventricular tissue recovered during lead extraction

Heart Rhythm. 2012 Mar;9(3):399-404. doi: 10.1016/j.hrthm.2011.10.019. Epub 2011 Oct 19.

Abstract

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Cardiac Pacing, Artificial / methods
  • Defibrillators, Implantable
  • Electrocardiography
  • Feasibility Studies
  • Female
  • Gene Expression
  • Genetic Markers
  • Genetic Testing / methods*
  • Genome-Wide Association Study
  • Heart Diseases / genetics*
  • Heart Diseases / pathology
  • Heart Diseases / therapy
  • Heart Transplantation / pathology
  • Humans
  • Male
  • Middle Aged
  • Myocytes, Cardiac / pathology*
  • Pacemaker, Artificial
  • Polymorphism, Single Nucleotide
  • Sodium-Calcium Exchanger / genetics
  • Time Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • Genetic Markers
  • NOS1AP protein, human
  • Sodium-Calcium Exchanger