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)

Several cytokines are activated in chronic heart failure (CHF), including interleukin-2 (IL-2). IL-2 is important for the survival of regulatory T cells, as well as for the function of activated T cells. Its role in ischemic cardiomyopathy has not yet been investigated. We therefore studied left ventricular (LV) performance and remodeling in a rat model of myocardial infarction (MI) after treatment with an IL-2IgG2b fusion protein to stimulate IL-2 signaling. Spraque-Dawley rats (SD) were submitted to permanent ligation of the left descending artery (LAD) to induce a MI or to a sham operation. Twenty-four hours, 6 days and 3 weeks after MI, LV function was determined in vivo using a tip catheter. Cardiac IL-2 and IL-1beta content was measured by immunohistochemical staining on cryo-fixed heart cross sections at 24h and 6 days post MI. Total collagen content of the LV was determined by Sirius red stained formalin-stored sections under circularly polarized light 3 weeks post MI. Compared to sham-operated animals, IL-2 content was increased 13-fold (P<0.01) 24h post MI and 16-fold (P<0.01) 6 days post MI in the infarction area as well as 2-fold (P<0.05) 6 days post MI in the non-infarction area. Despite similar infarct sizes, LV function and remodeling were ameliorated in IL-2 fusion protein-treated ischemic rats, indicated by improved LV pressure (LVP), contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)) at all three time points. LV collagen content as a surrogate parameter for remodeling and IL-1beta expression as a marker for myocardial inflammation were reduced in the non-infarcted LV, but not in the LV infarction area compared to vehicle-treated controls. LV contractile dysfunction after experimental MI is improved after treatment with an IL-2-IgG2b fusion protein.
 ...
PMID:Immunosuppression with an interleukin-2 fusion protein leads to improved LV function in experimental ischemic cardiomyopathy. 1989 56

High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T(2) weighted imaging and T(1) weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T(1) and T(2) weighted CMRI techniques to diagnose IL-2 induced myocarditis.
 ...
PMID:Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma. 2151 46

Accumulating evidence reveals involvement of T lymphocytes and adaptive immunity in the chronic inflammation associated with infectious and noninfectious diseases of the heart, including coronary artery disease, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, hypertensive left ventricular (LV) hypertrophy, and nonischemic heart failure. Chemokine CXCL10 is elevated in cardiovascular diseases, along with increased cardiac infiltration of proinflammatory Th1 and cytotoxic T cells. CXCL10 is a chemoattractant for these T cells and polarizing factor for the proinflammatory phenotype. Thus, targeting the CXCL10 receptor CXCR3 is a promising therapeutic approach to treating cardiac inflammation. Due to biased signaling CXCR3 also couples to anti-inflammatory signaling and immunosuppressive regulatory T cell formation when activated by CXCL11. Numbers and functionality of regulatory T cells are reduced in patients with cardiac inflammation, supporting the utility of biased agonists or biologicals to simultaneously block the pro-inflammatory and activate the anti-inflammatory actions of CXCR3. Other immunotherapy strategies to boost regulatory T cell actions include intravenous immunoglobulin (IVIG) therapy, adoptive transfer, immunoadsorption, and low-dose interleukin-2/interleukin-2 antibody complexes. Pharmacological approaches include sphingosine 1-phosphate receptor 1 agonists and vitamin D supplementation. A combined strategy of switching CXCR3 signaling from pro- to anti-inflammatory and improving Treg functionality is predicted to synergistically lessen adverse cardiac remodeling.
 ...
PMID:The CXCL10/CXCR3 Axis and Cardiac Inflammation: Implications for Immunotherapy to Treat Infectious and Noninfectious Diseases of the Heart. 2779 61

Interleukin (IL)-15 is a recently identified cytokine, which belongs to the interleukin-2(IL-2) family, and plays an important role in innate and adaptive immunoreaction. Given the fact that the structure of IL-15 is partially similar to IL-2, they share some common biological effects, including immunoregulation. IL-2 was proven to protect cardiac function in mouse myocardial infarction models. Cardiovascular diseases (CVDs) dominate the cause of mortality worldwide. Besides atherosclerosis, inflammation is also widely involved in the pathogenesis of many CVDs including hypertension, heart failure (HF) and aneurysm. IL-15, as a pro-inflammatory cytokine, is up-regulated in some cardiovascular diseases, such as myocardial infarction and atherosclerosis. The current understanding of IL-15, including its signal pathway and cellular function, was described. Furthermore, IL-15 has a protective effect in myocardial infarction and myocarditis by decreasing cardiomyocyte death and improving heart function. The inhibited effect of IL-15 in ductus arteriosus (DA) should be focused on. IL-15 promoted atherogenesis. IL-15 may be a good target in treatment of cardiovascular diabetology. Finally, future research direction of IL-15 deserves attention. Since IL-15 plays several roles in CVDs, understanding the role of the IL-15/IL-15R system may provide a scientific basis for the development of new approaches that use IL-15 for the treatment of CVDs.
 ...
PMID:Role of interleukin-15 in cardiovascular diseases. 3240 86


<< Previous 1 2 3