Abstract 16313: De-Activation of Mitogen-Activated Protein Kinases in Peripheral Blood Mononuclear Cells of Patients Undergoing Trans-Catheter Aortic Valve Implantation
Trans-catheter aortic valve implantation (TAVI) is a promising technique for patients with severe aortic stenosis (AS) and high surgical risk. Since we have previously shown that Mitogen Activated Protein Kinases (MAPKs) activity in peripheral blood cells is a sensitive marker of cardiac stress during in vivo pressure overload, in the present study we tested whether pressure unloading following TAVI could affect these molecular signal pathways in blood mononuclear cells. White blood cells (WBC) were isolated from patients before and after (48 hours) valve implantation (both trans-arterial or trans-apical, n=10). Extracellular signal-regulated kinase (ERK) and p38 (p38) phosphorylation was next evaluated by western blot. Age-matched patients without AS or arterial hypertension were used as controls (CTR, n=5). WBC isolated before TAVI displayed a significant activation of MAPKs compared to the control group (Figure). Interestingly, effective pressure unloading following TAVI was associated with MAPKs de-activation (pERK levels fold over control, PRE: 22.97 ± 6.25, POST: 8.72 ± 3.86; p-p38 levels fold over control, PRE: 7.26 ± 0.89, POST: 1.61 ± 0.45; for all, *p <0.05 vs. CTR). Furthermore, WBC isolated before TAVI displayed a significant activation of the beta-adrenergic receptor kinase 1 (GRK2), and this was reversed to control levels after valve implantation (GRK2 levels fold over control, PRE: 2.8 ± 0.44, POST: 0.8 ±0.53, p<0.05). Our data suggest that MAPKs are sensors of pressure overload, and that their expression in WBC might be used as a novel surrogate to predict LV response to valve implantation.
- © 2011 by American Heart Association, Inc.