Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy.

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 targeting of phospholamban, a key regulator of cardiac Ca(2+) homeostasis.

Cardiac-targeted RNA interference mediated by an AAV9 vector improves cardiac function in coxsackievirus B3 cardiomyopathy.

RNA interference (RNAi) has potential to be a novel therapeutic strategy in diverse areas of medicine. In this paper, we report on targeted RNAi for the treatment of a viral cardiomyopathy, which is a major cause of sudden cardiac death or terminal heart failure in children and young adults. RNAi therapy employs small regulatory RNAs to achieve its effect, but in vivo use of synthetic small interfering RNAs is limited by instability in plasma and low transfer into target cells.

Immunohistological detection of Parvovirus B19 capsid proteins in endomyocardial biopsies from dilated cardiomyopathy patients.

Background: Parvovirus B19 (B19V) has been identified as the most common virus in dilated cardiomyopathy (DCM) patients by PCR techniques. We investigated the detectability and the expression pattern of B19V proteins by immunohistology (IH) in endomyocardial biopsies (EMBs) from DCM patients, and its association with the standard proof of B19V genomes by nested PCR (nPCR.

Material/methods: EMBs from 30 DCM patients were analyzed by nPCR for B19V genomes, and IH of B19V VP1/VP2 expression was carried out using the antibody clone R92F6.

Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy.

Aims: Despite recent advances in medical therapy, heart failure remains a leading cause for cardiovascular mortality, and its complex pathogenesis is incompletely understood. This study was performed to identify possible new therapeutic targets in dilated cardiomyopathy (DCM).

Methods And Results: Oligonucleotide microarray analysis was performed on endomyocardial biopsies (EMBs) from patients with early DCM (LVEDD > or = 55 mm, LVEF < or = 55%, n = 5) and control subjects (LVEDD < 55 mm, LVEF > 60%, no cardiac pathology, n = 4).

Differential internalization and nuclear uncoating of self-complementary adeno-associated virus pseudotype vectors as determinants of cardiac cell transduction.

Recently it was shown that several new pseudotyped adeno-associated virus (AAV) vectors support cardioselective expression of transgenes. The molecular mechanisms underlying this propensity for cardiac cell transduction are not well understood. We comparatively analyzed AAV vector attachment, internalization, intracellular trafficking, and nuclear uncoating of recombinant self-complementary (sc) AAV2.