Extracellular matrix remodeling in early cardiac fibrosis and diastolic dysfunction

Background: Half of the patients with congestive heart failure suffer from diastolic dysfunction with persistent left ventricular function (HFpEF). Until today different explanations exist, but the exact mechanism of HFpEF is still unclear. From human biopsies and different animal models it is known that in HFpEF the extracellular matrix underlies remodeling processes with increased fibrosis and disturbance of cardiac architecture. Our study aimed to characterize changes of the extracellular matrix in early cardiac fibrosis and diastolic dysfunction. Methods: In C57Bl/6-mice, osmotic minipumps were implanted with a continuous infusion of Angiotensin II (Ang, 0.5μg/kg/min) or NaCl (Sham). After assessment of systolic and diastolic parameters using echocardiography at day 7 or 28, mice were euthanized (Ang7d, n=22/Ang28d, n=27/Sham, n=20). Cardiac tissue was investigated with micro array technology, western blot, qRT-PCR and immunohistochemistry. Results: Echocardiography revealed a reliable induction of diastolic dysfunction with persistent LVEF in the Ang groups (E/E': Sham 25.9±1.0 vs. Ang28d 38.5±4.4; p