Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Bironaitė, Daiva; Daunoravičius, Dainius; Bogomolovas, Julius; Čibiras, Sigitas; Vitkus, Dalius; Žurauskas, Edvardas; Zasytyte, Ieva; Ručinskas, Kęstutis; Labeit, Siegfried; Venalis, Algirdas; Grabauskienė, Virginija

doi:10.1186/s12872-015-0017-1

Cited by 21 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations agree with the polymorphisms analyzed in patients with idiopathic dilated cardiomyopathy (IDCM) that relates to TNF, IL-6, and CRP profile. A recent study shows that a rough increase in serum IL-6 is incidental with chronic IDCM [82].…”

Section: Interleukin-6mentioning

confidence: 99%

Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden

Kölliker-Frers¹,

Otero‐Losada²,

Razzitte³

et al. 2018

Chagas Disease - Basic Investigations and Challenges

View full text Add to dashboard Cite

The economic and social burden associated with Chagas disease morbidity and mortality is regrettably large in Latin America causing more deaths than does any other parasitic disease. Inflammatory dilated cardiomyopathy is, by far, the most important clinical consequence of Trypanosoma cruzi infection. The insidious persistence of this parasite determines chronic myocarditis progression. The clinical outcome is multifactorial and depends on the particular parasite strain and virulence factors, the infective load and route of infection, the parasite ability to by-pass the protective immune response, the intensity and type of immune response during the acute infective phase, and the host genetic background. From the immunological viewpoint, host control of T. cruzi has been shown to depend on both humoral and cell-mediated adaptive responses and from the innate immune system. In this review, we discuss the most relevant literature conveying information on the relevance of identifying a subset of systemic inflammatory molecules as potential markers of cardiovascular risk morbidity and mortality in patients with Chagas disease. Concurrently, a direct role for the parasite in the perpetuation of myocardial inflammation is substantiated. Ultimately, host-parasite interactions determine the course of the ongoing systemic inflammation and the perpetuation of myocardial inflammation in genetically predisposed patients.

show abstract

Section: Interleukin-6mentioning

confidence: 99%

Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden

Kölliker-Frers¹,

Otero‐Losada²,

Razzitte³

et al. 2018

Chagas Disease - Basic Investigations and Challenges

View full text Add to dashboard Cite

show abstract

“…Inflammation is a natural biological process that occurs during times of infection or wound healing and is self-limiting which is hence called acute inflammation. During chronic inflammation this self-limiting process is deregulated and can contribute to a number of diseases including: Alzheimer's [ 6 ], cardiomyopathy [ 7 ], osteoarthritis [ 8 ], inflammatory bowel disease (IBD) [ 9 ], and numerous types of cancers including breast [ 10 – 12 ]. Specifically, chronic inflammation has been associated with cancer initiation and progression [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Macrophage inflammatory factors promote epithelial-mesenchymal transition in breast cancer

et al. 2018

View full text Add to dashboard Cite

The majority of breast cancers (90–95%) arise due to mediators distinct from inherited genetic mutations. One major mediator of breast cancer involves chronic inflammation. M1 macrophages are an integral component of chronic inflammation and the breast cancer tumor microenvironment (TME). Previous studies have demonstrated that up to 50% of the breast tumor comprise of tumor-associated macrophages (TAMs) and increased TAM infiltration has been associated with poor patient prognosis. Furthermore, breast cancer associated deaths are predominantly attributed to invasive cancers and metastasis with epithelial-mesenchymal transition (EMT) being implicated. In this study, we investigated the effects of cellular crosstalk between TAMs and breast cancer using an in vitro model system. M1 polarized THP-1 macrophage conditioned media (CM) was generated and used to evaluate cellular and functional changes of breast cancer lines T47D and MCF-7. We observed that T47D and MCF-7 exhibited a partial EMT phenotype in the presence of activated THP-1 CM. Additionally, MCF-7 displayed a significant increase in migratory and invasive properties. We conclude that M1 secretory factors can promote a partial EMT of epithelial-like breast cancer cells. The targeting of M1 macrophages or their secretory components may inhibit EMT and limit the invasive potential of breast cancer.

show abstract

“…Numerous epidemiological studies have identified cardiac inflammation and insulin resistance as independent risk factors for the development of heart failure 11,17,56,57 . However, little is known about the relationship between these factors in terms of the mechanism involved in cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Improvement of insulin signalling rescues inflammatory cardiac dysfunction

Al-Huseini

Harada

Nishi

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Inflammation resulting from virus infection is the cause of myocarditis; however, the precise mechanism by which inflammation induces cardiac dysfunction is still unclear. In this study, we investigated the contribution of insulin signalling to inflammatory cardiac dysfunction induced by the activation of signalling by NF-κB, a major transcriptional factor regulating inflammation. We generated mice constitutively overexpressing kinase-active IKK-β, an essential kinase for NF-κB activation, in cardiomyocytes (KA mice). KA mice demonstrated poor survival and significant cardiac dysfunction with remarkable dilation. Histologically, KA hearts revealed increased cardiac apoptosis and fibrosis and the enhanced recruitment of immune cells. By molecular analysis, we observed the increased phosphorylation of IRS-1, indicating the suppression of insulin signalling in KA hearts. To evaluate the contribution of insulin signalling to cardiac dysfunction in KA hearts, we generated mice with cardiac-specific suppression of phosphatase and tensin homologue 10 (PTEN), a negative regulator of insulin signalling, in the KA mouse background (KA-PTEN). The suppression of PTEN successfully improved insulin signalling in KA-PTEN hearts, and interestingly, KA-PTEN mice showed significantly improved cardiac function and survival. These results indicated that impaired insulin signalling underlies the mechanism involved in inflammation-induced cardiac dysfunction, which suggests that it may be a target for the treatment of myocarditis.

show abstract

Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Cited by 21 publications

References 41 publications

Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden

Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden

Macrophage inflammatory factors promote epithelial-mesenchymal transition in breast cancer

Improvement of insulin signalling rescues inflammatory cardiac dysfunction

Contact Info

Product

Resources

About