Myocardial expression of Toll‐like receptor 4 predicts the response to immunosuppressive therapy in patients with virus‐negative chronic inflammatory cardiomyopathy

Chimenti, Cristina; Verardo, Romina; Scopelliti, Fernanda; Grande, Claudia Del; Petrosillo, Nicola; Piselli, Pierluca; Paulis, Ruggero De; Frustaci, Andrea

doi:10.1002/ejhf.796

Cited by 35 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although a broader use to improve the diagnosis of myocarditis and inflammatory cardiomyopathy has recently been proposed, many statements reserved the indications to endomyocardial biopsy for selected cases . In a patient with newly diagnosed DCM, endomyocardial biopsy is reasonable when there is a high probability of a specific diagnosis which can be confirmed only in myocardial samples and is amenable to therapy that has the potential to change the course of the disease . Examples of such scenarios include active myocarditis ( Figure ), the contemporary presence of a hypertrophic and dilated left ventricle (for example in end‐stage hypertrophic cardiomyopathy), cardiac amyloidosis, sarcoidosis, or haemochromatosis …”

Section: Specific Aspects In the Clinical Management Of Dilated Cardimentioning

confidence: 99%

Evolving concepts in dilated cardiomyopathy

Merlo

Cannatà

Gobbo

et al. 2017

European J of Heart Fail

279

270

View full text Add to dashboard Cite

Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co-morbidities. The prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red-flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non-pharmacological evidence-based treatments. However, some important issues in clinical management remain unresolved, including the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review offers a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.

show abstract

Section: Specific Aspects In the Clinical Management Of Dilated Cardimentioning

confidence: 99%

Evolving concepts in dilated cardiomyopathy

Merlo

Cannatà

Gobbo

et al. 2017

European J of Heart Fail

279

270

View full text Add to dashboard Cite

show abstract

“…Heart tissue samples were treated as described [11]. The expression of myocardial aldosterone receptors and Aquaporin 1 and 4 was visualized by using mineralocorticoid receptor monoclonal antibody (1:500), anti-Aqp1 (1:100) and anti-Aqp4 (1: 200).…”

Section: Protein Isolation and Western Blotmentioning

confidence: 99%

Primary aldosteronism-associated cardiomyopathy: Clinical-pathologic impact of aldosterone normalization

Frustaci

Letizia

Verardo

et al. 2019

International Journal of Cardiology

Self Cite

View full text Add to dashboard Cite

Background: Primary aldosteronism (PA) causes a cardiomyopathy (CM) which substrate and evolution after aldosterone normalization are unreported. Methods: Four male patients with aldosterone-secreting adrenal adenoma and cardiomyopathy (PACM, group A) were evaluated with 2D-echo, Magnetic Resonance (CMR), coronary angiography and left ventricular endomyocardial biopsy. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western Blot analysis of myocardial aldosterone receptors and aquaporin 1 and 4. Results were compared with endomyocardial samples from 5 patients with hypertensive cardiomyopathy of equivalent severity and normal plasma aldosterone (group B) and surgical samples from 5 controls (group C). One PACM patient was re-examined with CMR and endomyocardial biopsy 12 months after adrenalectomy with aldosterone and cardiac normalization. Results: Coronary arteries were normal in all. Group A showed prominent myocardial hypertrophy and fibrosis, with water accumulation in the cytosol and organelles of cardiomyocytes and microvascular smooth muscle cells, associated to reduced myofibril concentration and 2.8-fold increase in myocardial aldosterone receptors and aquaporin 1. At CMR, LGE areas were diffusely present. After aldosterone normalization, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles, recovery of electron-density of cytosol and cell organelles, and myofibrillar content, persisting fibrosis and down-regulation of aldosterone receptors and aquaporin 1 channels. At CMR, myocardial mass reduced with recovery of cardiac contractility. LGE signal remained unchanged. Conclusion: PACM is a reversible entity characterized by over-expression of aldosterone receptors and aquaporin 1. It induces a reversible intracellular water overloading causing impaired cardiomyocyte relaxation, contraction and ultrastructural integrity.

show abstract

“…Toll-like receptor 4 (TLR4), the first described member of the TLR family, mediates the inflammatory response in the myocardium; in addition, its mediated inflammatory signaling pathway plays a key role in myocarditis, myocardial infarction, and ischemia-reperfusion injury [7][8][9]. Multiple studies have demonstrated that TLR4/MyD88/NF-κB signaling controls the production of proinflammatory factors and induces the inflammatory response in the myocardial tissues, which is the main cause of myocardial tissue injury [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury

Sun

et al. 2018

Cell Physiol Biochem

154

101

View full text Add to dashboard Cite

Background/Aims: Coronary microembolization (CME) is a common complication of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI); Myocardial inflammation, caused by CME, is the main cause of cardiac injury. TLR4/MyD88/NF-κB signaling plays an important role in the development of myocardial inflammation, but its effects on CME remain unclear. To assess the cardiac protective effects of TAK-242 (TLR4 specific inhibitor) on CME-induced myocardial injury, and explore the underlying mechanism. Methods: Cardiac function, serum c-troponin I level, microinfarct were examined by cardiac ultrasound, myocardial enzyme assessment, HBFP staining. The levels of TLR4/MyD88/NF-κB signaling and NLRP3 inflammasome pathway were detected by ELISA, qRT-PCR and western blot. Results: The results showed inflammatory responses in the myocardium after CME, with increased expression levels of pro-inflammatory factors TNF-α, IL-1β and IL-18. Meanwhile, TLR4/MyD88/NF-κB signaling and the NLRP3 inflammasome were involved in the inflammatory process. TAK-242 administration before CME effectively inhibited the inflammatory response in the rat myocardium after CME and reduced myocardial injury, mainly by inhibiting TLR4/ MyD88/NF-κB signaling and reducing NLRP3 inflammasome activation. In addition, in vitro assays with neonatal rat cardiomyocytes further confirmed that TLR4/MyD88/NF-κB signaling was significantly activated in the inflammatory response of LPS-induced cardiomyocytes, via activation of the NLRP3 inflammasome. Inhibition of TLR4/MyD88/NF-κB signaling resulted in increased survival of cardiomyocytes mainly by reducing the release of inflammatory cytokines and decreasing NLRP3 inflammasome activation. Conclusions: TLR4/MyD88/NF-κB signaling participates in the inflammatory response of the myocardium after CME, activating the NLRP3 inflammasome, promoting the inflammatory cascade, and aggravating myocardial injury. Blocking TLR4/MyD88/NF-κB signaling may help reduce myocardial injury and improve cardiac function after CME.

show abstract

Myocardial expression of Toll‐like receptor 4 predicts the response to immunosuppressive therapy in patients with virus‐negative chronic inflammatory cardiomyopathy

Abstract: TLR4 is highly expressed in human myocarditis responding to immunosuppression. It can be considered as a new sensitive marker in patient selection predicting a good response to immunosuppressive therapy.

Cited by 35 publications

References 30 publications

Evolving concepts in dilated cardiomyopathy

Evolving concepts in dilated cardiomyopathy

Primary aldosteronism-associated cardiomyopathy: Clinical-pathologic impact of aldosterone normalization

Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury

Contact Info

Product

Resources

About