Histopathological Features and Mitochondrial (mt-) DNA Abundance Correlate with Energy Starvation in Congestive Heart Failure (CHF)
S He, P Zhao, JJ Kohler, N Patel, E Green, SH Hosseini, J Butler, AM Samarel, W Lewis. Emory University School of Medicine, Atlanta, GA; Loyola University Medical Center, Maywood, IL
Background: Myocardial energy starvation in CHF suggests that defective mitochondrial oxidative phosphorylation leads to defective cardiac contractility. We hypothesize that decreased mitochondrial abundance in cardiomyocytes causes energy starvation in CHF by decreasing abundance of mitochondrially encoded elements of the electron transport chain and correlates with histopathological features of CHF.
Design: Human cardiac samples were obtained fresh at the time of orthotopic heart transplantation (under IRB approval) at Emory University and Loyola University Medical Center using standard protocols. CHF samples were classified clinically as ischemic (I; n=24), and non-ischemic (NI; n=21). Samples from non-failing (NF; n=12) hearts were obtained as controls. Samples of left ventricle (LV) myocardium were flash-frozen individually and stored (-80°C). DNA was extracted individually using a high-throughput automation DNA extraction. Steady state abundance of mtDNA and nuclear DNA (nDNA) was determined for each LV sample using Real-Time PCR. mtDNA/nDNA ratios were derived. Data were analyzed statistically and expressed as log10 mtDNA/nDNA ratios of LV extracts (CHF vs. NF). Parallel samples were fixed in formalin and evaluated quantitatively for average nuclear area and cytoplasmic area for each sample (repeated 20 times) using Image J Software (NIH).
Results: CHF Patients with I or NI exhibited decreased LV mtDNA compared to those from NF (p<0.05 ANOVA). Histopathological data revealed decreased myocyte volume and decreased nuclear volume in samples from CHF hearts (p<0.01).
Conclusions: CHF relates inversely to steady-state mtDNA abundance and nuclear volume. Data support the concept that defective mitochondrial biogenesis is critical to CHF and to the morphological changes seen in CHF.
Monday, March 22, 2010 11:15 AM
Platform Session: Section G 2, Monday Morning