Gene and Protein Expression in the Myocardium Varies with Duration of Mechanical Circulatory Assistin Heart Failure Patients.
Anna Meredith, Amrit Samra, Lise Matzke, Crystal Leung, Bruce McManus. University of British Columbia, Vancouver, Canada
Background: Introduction: Management of the failing heart involves medical therapy, mechanical circulatory assist(MCA) devices and heart transplantation. Unloading of the heart by MCA may induce reverse remodeling andnormalize cardiac parameters (cardiac chamber geometry, size, volume, ejection fraction and fetal gene expression).We undertook to identify gene and protein markers of heart failure and determine “fetal” gene and proteinexpression within the heart upon MCA. We examined the hypothesis that expression changes over timecorresponding to the duration of circulatory support with MCA.
Design: Methods: Left ventricular (LV) apical tissue cores removed during LV assist device (LVAD) implantation, andcorresponding explanted hearts obtained at the time of transplantation were examined. Tissues from seven patientswith a mean age of 55.6 ± 5.4 years were analyzed. Serial sections were prepared with standard histology stainsfor quantification of myocardial fibrosis and remodeling. Immunohistochemical staining for markers of myocardialdysfunction and remodeling (brain natriuretic peptide, galectin-3, versican, matrix metalloproteinases 2 and 9) wasperformed. Extracted RNA was analyzed on Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays and byquantitative PCR for α-myosin heavy chain, β-myosin heavy chain and phospholamban. Differential staining, geneexpression and degree of remodeling were quantified and correlated with duration of MCA. Comparison was alsomade of gene and protein signatures from LV core samples at time of LVAD implant with apical LV samples fromcorresponding explanted hearts.
Results: Results: Deleterious LV remodeling and alterations in contractile function in HF are associated withchanges in gene and protein expression, including activation of the “fetal” gene program, and dysregulatedexpression of fibrotic markers. Unloading of the heart through MCA results in decreases in myocyte hypertrophyand myocardial fibrosis with concomitant changes in gene and protein expression.
Conclusions: In conclusion, the extent of geneand protein expression alteration is a function of duration of mechanical unloading, and a time dependent alterationin relevant markers exists.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 45, Monday Morning