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BACKGROUND RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. Here, we report on targeted RNAi for the treatment of heart failure, an important disorder in humans that results from multiple causes. Successful treatment of heart failure is demonstrated in a rat model of transaortic banding by RNAi(More)
Background—Increased left ventricular stiffness is a distinct finding in patients who have heart failure with normal ejection fraction (HFNEF). To elucidate how diastolic dysfunction contributes to heart failure symptomatology during exercise, we conducted a study using an invasive pressure-volume loop approach and measured cardiac function at rest and(More)
BACKGROUND Cardiac inflammation and generation of oxidative stress are known to contribute to doxorubicin (Dox)-induced cardiomyopathy. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signalling, we investigated whether or not TLR4(More)
AIMS Diastolic heart failure is a frequent entity but difficult to diagnose. N-terminal pro-B type natriuretic peptide (NT-proBNP) was therefore investigated as a possible non-invasive parameter to diagnose isolated diastolic dysfunction. METHODS AND RESULTS Sixty-eight symptomatic patients with isolated diastolic dysfunction and preserved left(More)
Doxorubicin is a frequently used anticancer drug, but its therapeutic benefit is limited by acute and chronic cardiotoxicity, often leading to heart failure. The mechanisms underlying doxorubicin-induced cardiotoxicity remain unclear. It was previously shown in men that doxorubicin leads to increased endothelin-1 plasma levels. In addition, cardiac-specific(More)
Diabetic cardiomyopathy includes fibrosis. Kallikrein (KLK) can inhibit collagen synthesis and promote collagen breakdown. We investigated cardiac fibrosis and left ventricular (LV) function in transgenic rats (TGR) expressing the human kallikrein 1 (hKLK1) gene in streptozotocin (STZ) -induced diabetic conditions. Six weeks after STZ injection, LV function(More)
BACKGROUND Various conventional and tissue Doppler echocardiographic indexes were compared with pressure-volume loop analysis to assess their accuracy in detecting left ventricular (LV) diastolic dysfunction in patients with heart failure with normal ejection fraction (HFNEF). METHODS AND RESULTS Diastolic dysfunction was confirmed by pressure-volume loop(More)
BACKGROUND Angiopoietin-1 (Ang1) plays an essential role in embryonic vasculature development, protects the adult peripheral vasculature from leakage, and has antiinflammatory properties. Because endotoxin-induced shock is a condition with microvascular leakage resulting from inflammation, we examined the potential therapeutic benefit of Ang1 in a murine(More)
BACKGROUND The progressive shift from a young to an aged heart is characterized by alterations in the cardiac matrix. The present study investigated whether the matricellular protein thrombospondin-2 (TSP-2) may affect cardiac dimensions and function with physiological aging of the heart. METHODS AND RESULTS TSP-2 knockout (KO) and wild-type mice were(More)