Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Favorable effects of angiotensin II type 1 receptor blockers on patients with ischemic or idiopathic dilated cardiomyopathy have already been suggested by several human trials but their effects on inflammatory cardiomyopathy remain unknown. We investigated the effects of the angiotensin II type 1 receptor blocker, valsartan, in chronic heart failure after inflammatory cardiomyopathy. Autoimmune myocarditis was induced in Lewis rats by injection with porcine cardiac myosin. In the phase of chronic heart failure, from day 28 until day 70, rats were treated by oral administration of valsartan. Three groups were designated: 1 ml saline, 10 mg/kg valsartan, and 30 mg/kg valsartan. On the 73rd day, hemodynamic parameters, pathological findings and the expression levels of r-ANP mRNA of the ventricle were examined, and were compared with the saline control. The ventricular weight/body weight ratio and area of fibrosis was decreased in the 30 mg/kg valsartan group. The left ventricular end-diastolic pressure and the central venous pressure were decreased in a dose-dependent manner in both valsartan groups, while the first pressure derivatives +dP/dt and -dP/dt did not differ among the three groups. A high dose of valsartan reduced the expression of tissue ANP mRNA compared with the saline group. In conclusion,valsartan suppressed myocardial hypertrophy and fibrosis, and it improved the hemodynamics and cardiac function in an animal model of post-myocarditis dilated cardiomyopathy.
 ...
PMID:Angiotensin II type 1 receptor blocker, valsartan, prevented cardiac fibrosis in rat cardiomyopathy after autoimmune myocarditis. 1268 5

Autoimmune responses and inflammation are involved in the excess cardiovascular risk observed in patients with systemic inflammatory diseases. Autoimmune myocarditis is a presentation of an inflammatory reaction of the heart during the course of autoimmune disorders, with most cases seen in systemic lupus erythematosus. Early diagnosis is of great significance because of the likelihood of progression to severe and potentially fatal complications such as arrhythmias, heart block, and heart failure. The clinical presentation of the disease is silent leading to delayed diagnosis when dilated cardiomyopathy or heart failure has already advanced. Therefore, a major issue is whether the diagnosis of myocarditis will continue to require invasive procedures such as endomyocardial biopsy or can be achieved with non-invasive methods. There is increasing evidence that noninvasive cardiac imaging, including tissue Doppler echocardiography and cardiac magnetic resonance (CMR), is able to detect subclinical cases and aid in the initiation of specific treatment when it is more likely to be effective. CMR in particular, has emerged as an important technique in the evaluation of myocarditis using three types of images: T2-weighted (T2-W), early T1-weighted (EGE) images taken after 1 min, and delayed enhanced images (LGE) taken 15 min after the injection of contrast agent. If 2/3 of the imaging sequences are positive, myocardial inflammation can be predicted or ruled out with a diagnostic accuracy of 78%. As our understanding of disease mechanisms improves, multimodality imaging may aid in the development of new diagnostic and therapeutic strategies for this potentially devastating complication of systemic inflammation, but further studies are needed to formally evaluate this.
 ...
PMID:Multimodality imaging and the emerging role of cardiac magnetic resonance in autoimmune myocarditis. 2261 20

Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens.
...
PMID:Learning from myocarditis: mimicry, chaos and black holes. 2490 49

Autoimmune myocarditis is a cause of dilated cardiomyopathy and heart failure. MicroRNAs regulate many immune processes, but their role in aberrant inflammation during autoimmune myocarditis remains unclear. In this study, we investigated the role of miR-223-3p in experimental autoimmune myocarditis (EAM). We found that miR-223-3p expression was significantly lower in EAM mice than that in normal mice. miR-223-3p inhibited NLRP3 inflammasome expression, promoting the polarization of dendritic cells (DCs) towards a tolerogenic DC phenotype. miR-223-3p effectively induced regulatory T cell (Treg) generation by inhibiting the function of antigen-presenting DCs. Transfer of miR-223-3p-overexpressing DCs protected mice against the development of EAM. Our findings suggest that miR-223-3p is involved in the induction of the tolerogenic DC phenotype and regulates tolerance in autoimmune myocarditis.
 ...
PMID:MicroRNA-223-3p modulates dendritic cell function and ameliorates experimental autoimmune myocarditis by targeting the NLRP3 inflammasome. 3174 55