Abstract 20054: Myocardial Expression and Circulating Serum Levels of the Extracellular Matrix Markers MMP-2, MMP-9 and Osteopontin in Patients with Advanced Heart Failure Undergoing Ventricular Assist Device Placement
Cardiac fibrosis, inflammation and increased matrix turnover develop in heart failure (HF). Ventricular assist devices (VAD) offer new therapeutic options for patients with advanced HF. We hypothesized that mechanical unloading of the failing heart through implantation of VAD changes myocardial expression and circulating levels of biomarkers of matrix remodeling. Myocardium and serum was obtained from 39 patients with HF undergoing VAD implantation and explantation and 10 controls. Clinical data were obtained from medical records. mRNA expression was analyzed by RT-PCR. Circulating levels of osteopontin (OPN), MMP-2, MMP-9, TIMP-1 and TIMP-4 were measured by ELISA. The cohort had a mean BMI of 27.1±5.1 kg/m2, age of 51±12.0 yrs and mean VAD duration of 185±156.2 days. 17 pulsatile devices and 22 non-pulsatile VADs were placed. Reduced myocardial expression of MMP-2 (−50%), MMP-9 (−39%) and OPN (−25%) was found after VAD placement (all p<0.05). Serum analysis showed increased levels of OPN (21.2±9.8 vs 271.4±187.1 ng/mL; p<0.0005), MMP-2 (218.8±32.6 vs 289.6±92.3 ng/mL; p<0.05) and MMP-9 (406.3±273.3 vs 733.4±452.2 ng/mL; p<0.05) in HF compared to controls. VAD implantation reduced serum MMP-2 (289.6+/−92.3 vs 253.4±100.1 ng/mL; p<0.05) and MMP-9 (723.0±459.0 vs 377.8±281.5 ng/mL; p<0.001) without significant changes in serum OPN (271.4±187.1 vs 244.1±124.4 ng/mL; p=NS). Comparison of serum markers in patients with pulsatile vs non-pulsatile VAD revealed a significant reduction of osteopontin levels only in patients with a pulsatile VAD (−36%; p=0.05) while OPN showed a mild increase in non-pulsatile VADs (+23%; p=NS). Our data demonstrate a distinct transcriptional profile of extracellular matrix genes after VAD implantation. These are reflected by a reduction in circulating levels of biomarkers elevated in HF patients such as MMP-2 and -9 and OPN. The type of VAD and its flow profile is associated with different profiles in serum biomarkers e.g. OPN which might reflect different molecular response mechanisms. Our data suggest that myocardial inflammation and matrix turnover can be reversed through mechanical unloading of the failing heart. In addition, they suggest that circulating biomarkers can be used to track these remodeling processes.
- © 2010 by American Heart Association, Inc.