Journal - Physiological Genomics

Abstract :

Physiological Genomics 13:25-30 (2003) 1094-8341/03 $5.00 © 2003 American Physiological Society Coronary artery disease (CAD) is the leading cause of mortalityand morbidity in developed nations. We hypothesized that CADis associated with distinct patterns of protein expression inthe coronary arteries, and we have begun to employ proteomicsto identify differentially expressed proteins in diseased coronaryarteries. Two-dimensional (2-D) gel electrophoresis of proteinsand subsequent mass spectrometric analysis identified the ferritinlight chain as differentially expressed between 10 coronaryarteries from patients with CAD and 7 coronary arteries fromnormal individuals. Western blot analysis indicated significantlyincreased expression of the ferritin light chain in the diseasedcoronary arteries (1.41 vs. 0.75; P = 0.01). Quantitative real-timePCR analysis showed that expression of ferritin light chainmRNA was decreased in diseased tissues (0.70 vs. 1.17; P = 0.013),suggesting that increased expression of ferritin light chainin CAD coronary arteries may be related to increased proteinstability or upregulation of expression at the posttranscriptionallevel in the diseased tissues. Ferritin light chain proteinmediates storage of iron in cells. We speculate that increasedexpression of the ferritin light chain may contribute to pathogenesisof CAD by modulating oxidation of lipids within the vessel wallthrough the generation of reactive oxygen species. Our resultsprovide in situ proteomic evidence consistent with the "ironhypothesis," which proposes an association between excessiveiron storage and a high risk of CAD. However, it is also possiblethat the increased ferritin expression in diseased coronaryarteries is a consequence, rather than a cause, of CAD.