Authors: Haig Aghajanian, Toru Kimura, Joel G Rurik...

Fibrosis is observed in nearly every form of myocardial disease. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure. However, clinical interventions and therapies that target fibrosis remain limited. Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8 T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts-fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease.

Topics: Animals; Antigens, Surface; CD8-Positive T-Lymphocytes; Endomyocardial Fibrosis; Fibroblasts; Humans; Immunotherapy, Adoptive; Male; Mice; Ovalbumin; Wound Healing

PubMed: 31511695
DOI: 10.1038/s41586-019-1546-z

Review

Authors: Hitoshi Kurose

Cardiac fibrosis is the excess deposition of extracellular matrix (ECM), such as collagen. Myofibroblasts are major players in the production of collagen, and are differentiated primarily from resident fibroblasts. Collagen can compensate for the dead cells produced by injury. The appropriate production of collagen is beneficial for preserving the structural integrity of the heart, and protects the heart from cardiac rupture. However, excessive deposition of collagen causes cardiac dysfunction. Recent studies have demonstrated that myofibroblasts can change their phenotypes. In addition, myofibroblasts are found to have functions other than ECM production. Myofibroblasts have macrophage-like functions, in which they engulf dead cells and secrete anti-inflammatory cytokines. Research into fibroblasts has been delayed due to the lack of selective markers for the identification of fibroblasts. In recent years, it has become possible to genetically label fibroblasts and perform sequencing at single-cell levels. Based on new technologies, the origins of fibroblasts and myofibroblasts, time-dependent changes in fibroblast states after injury, and fibroblast heterogeneity have been demonstrated. In this paper, recent advances in fibroblast and myofibroblast research are reviewed.

Topics: Animals; Cardiotonic Agents; Cell Differentiation; Cell Lineage; Collagen; Cytokines; Discoidin Domain Receptor 2; Endomyocardial Fibrosis; Extracellular Matrix; Fibroblasts; Gene Expression Regulation; Humans; Macrophages; Myocardium; Myocytes, Cardiac; Myofibroblasts; Signal Transduction

PubMed: 34359886
DOI: 10.3390/cells10071716

Authors: Paulo Sampaio Gutierrez, Fernando Peixoto Ferraz de Campos

PubMed: 29043203
DOI: 10.4322/acr.2017.024

Review

Authors: M S Valiathan

Topics: Biopsy; Echocardiography; Endocardium; Endomyocardial Fibrosis; Humans; Mitral Valve; Palliative Care; Tricuspid Valve

PubMed: 7694719
DOI: No ID Found

Authors: Joanne S Sutter, Tisha M Suboc, Anupama K Rao...

Tropical endomyocardial fibrosis is a common cause of restrictive cardiomyopathy worldwide, but is relatively rare in developed countries. We present a case of tropical endomyocardial fibrosis with right ventricular involvement initially mistaken as Ebstein's anomaly. We highlight the need for timely and accurate diagnosis to ensure appropriate management. ().

PubMed: 34317354
DOI: 10.1016/j.jaccas.2020.02.020

Authors: Tomonobu Yanase, Tomohiro Nakamura, Yumiko Haraguchi...

Endomyocardial fibrosis (EMF) is a rare restrictive cardiomyopathy in developed countries. The prognosis of EMF depends on severity of heart failure, and it is generally poor as there is no proven specific effective therapy. We have experienced a rare case of EMF in an elderly Japanese man.

PubMed: 31312583
DOI: 10.1002/jgf2.246

Authors: Maurizio Pieroni, Francesca Marzo, Costantino Smaldone...

Topics: Adult; Electrocardiography; Endomyocardial Fibrosis; Humans; Male; Tricuspid Valve Insufficiency; Ultrasonography

PubMed: 20466198
DOI: 10.1016/j.jacc.2009.06.072

Authors: Matthew J Flanigan, Michael R Velez, Emily A Ruden...

Topics: Aged; Endocarditis; Endomyocardial Fibrosis; Humans; Magnetic Resonance Imaging; Male; Ultrasonography, Doppler

PubMed: 28846127
DOI: 10.7556/jaoa.2017.115

Authors: Siddiq Ibrahim Khalil, Suha Khalil, Salma El Tigani...

OBJECTIVE

Endomyocardial fibrosis (EMF) is a rare disease and is often an underdiagnosed and forgotten cardiomyopathy. The objective of this study was to document the current frequency of EMF in Sudan by defining and selecting cases from patients attending the echocardiography laboratory. Additionally we aimed to create an EMF registry for Sudan.

METHODS

The study started in January 2007 and is on-going. All the patients attending our echocardiography clinics in four different hospitals in Khartoum, Sudan, were included. Transthoracic echocardiography was used as the main diagnostic and selection tool. The diagnosis of EMF was based on predefined criteria and definitions, and was further supported by additional clinical, ECG, laboratory and chest X-ray findings.

RESULTS

Out of 4 332 cases studied, 23 (0.5%) were found to have features of EMF. Females constituted 52% and the age range was 24 to 67 years. All patients presented with dyspnoea grades III-IV. Advanced heart failure with gross fluid overload was seen in 54% of cases and ascites was seen in 30%. EMF was biventricular in 53%, left ventricular in 29% and right ventricular in 18% of cases. Apical and ventricular wall fibrosis was found in all cases, followed by atrial enlargement, atrioventricular valve incompetence, ventricular cavity obliteration, restrictive flow pattern and pericardial effusion. Additional echocardiographic features are defined and discussed.

CONCLUSION

Although a rare disease, cases of EMF can be identified in Sudan if a high index of suspicion is observed. New echocardiographic features of ventricular wall layering, endocardial fibrous shelf and endomyocardiopericarial fibrosis were identified and are discussed.

Topics: Adult; Aged; Disease Management; Echocardiography; Endomyocardial Fibrosis; Female; Follow-Up Studies; Heart Ventricles; Humans; Incidence; Male; Middle Aged; Prospective Studies; Sudan; Young Adult

PubMed: 28906536
DOI: 10.5830/CVJA-2016-079

Review

Authors: Amy D Bradshaw, Kristine Y DeLeon-Pennell

Inflammation contributes to the development of heart failure (HF) through multiple mechanisms including regulating extracellular matrix (ECM) degradation and deposition. Interactions between cells in the myocardium orchestrates the magnitude and duration of inflammatory cell recruitment and ECM remodeling events associated with HF. More recently, studies have shown T-cells have signficant roles in post-MI wound healing. T-cell biology in HF illustrates the complexity of cross-talk between inflammatory cell types and resident fibroblasts. This review will focus on T-cell recruitment to the myocardium and T-cell specific factors that might influence cardiac wound healing and fibrosis in the heart with consideration of age and sex as important factors in T-cell activity.

Topics: Age Factors; Antigens, CD; Cell Communication; Cytokines; Endomyocardial Fibrosis; Extracellular Matrix; Female; Fibroblasts; Gene Expression Regulation; Heart Failure; Humans; Inflammation; Macrophages; Male; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Signal Transduction; T-Lymphocytes

PubMed: 32438054
DOI: 10.1016/j.matbio.2020.04.001