Abstract 14409: Myocardial Angiogenic Signature is Altered in Human Pressure Overload Hypertrophy and Congestive Heart Failure
Background. Experimental studies suggest a critical role of impaired angiogenesis in heart failure development.
Aim. To study whether altered fibroblast growth factor-2 (FGF2) and placental growth factor (PlGF) dependent signaling is associated with HF development in patients (pts) with pressure overload hypertrophy due to aortic stenosis (AS) and cardiomyopathy (CCMP).
Methods. Transcriptional signatures of FGF2, PlGF, and their respective receptors FGF2-receptor 1 and FLT1 were studied in left ventricular (LV) myocardial biopsies (control, C=13, AS=12, CCMP=18) and whole blood (C=10, AS=27, CCMP=18) using real-time PCR (relative units). FGF2 and PlGF serum levels were determined by ELISA in 10 controls, 24 AS and 18 CCMP patients.
Results (Table). Both gene expression and serum levels of FGF2 and PlGF were reduced in CCMP pts compared to C (p<0.001 by ANOVA). In AS pts, LV FGF2 and PlGF message levels were lower in those with EF<60% (n=6) vs those with preserved (n=6) LV function (3.8±1.1 vs 10.2±2 and 0.5±0.1 vs 1.9±0.4 respectively, both p<0.01). Note, the expression of the FGF2 receptor 1 and PlGF receptor FLT1 were decreased in CCMP pts compared to C (8.6±1.1 vs 14.1±2.2 and 0.9±0.1 vs 1.2±0.1, respectively, both p<0.01). In the cohort of patients with both serum and tissue analyses (n=42), a positive correlation was noted between circulating serum levels and myocardial gene expression of both FGF (r=0.41;p=0.03) and PlGF (r=0.42;p=0.03). No differences in whole blood gene expression were noted.
Conclusion. Myocardial FGF2 and PlGF gene expression as well as their circulating levels are reduced in patients with congestive cardiomyopathy and in patients with decompensated pressure overload due to aortic stenosis. Impaired angiogenic signaling may contribute to progression of human heart failure and represent a novel pathogenetic mechanism for targeted interventions. *p<0.05 vs C; **p<0.01 vs C; ***p<0.001 vs C; ##p<0.01 vs AS (ANOVA)
- © 2012 by American Heart Association, Inc.