Abstract
Systemic sclerosis (SSc) is rare, severe connective tissue disease characterized by endothelial and vascular damage, immune activation, and resulting in inflammation and fibrosis of skin and internal organs, including the heart. SSc is associated with high morbidity and mortality. Cardiac involvement is frequent in SSc patients, even though often asymptomatic at early stages, and represents one of the major causes of SSc-related mortality. Heart involvement has a variable clinical presentation, and its pathogenesis is not completely understood. Myocardial fibrosis is traditionally considered the immunopathologic hallmark of heart involvement in SSc. This unique histological feature is paralleled by distinctive clinical and prognostic features. The so-called “vascular hypothesis” represents the most credited hypothesis to explain myocardial fibrosis. More recently, the prominent role of an inflammatory myocardial process has been identified as a cardinal event in the evolution to fibrosis, thus also delineating an “inflammation-driven pathway to fibrosis”. The pro-inflammatory cytokine interleukin (IL)-1 has an apical and cardinal role in the myocardial inflammatory cascade and in cardiac dysfunction. The primary aim of this perspective article is: to present the emerging evidence on the role of IL-1 and inflammasome in both SSc and heart inflammation, to review the complex interplay between cellular metabolism and inflammasome activation, and to discuss the rationale for targeted inhibition of IL-1 for the treatment of SSc-heart involvement, providing preliminary experimental and clinical data to support this hypothesis.
Highlights
Heart involvement is frequent and is a major cause of mortality in systemic sclerosis (SSc), being responsible for up to 30% of disease-related deaths [1,2,3]
Interleukin-1 and Systemic Sclerosis inflammatory myocardial disease, myocardial fibrosis is usually considered the immunopathologic hallmark of SSc heart disease
The fact that only the inflammatory pathway to fibrosis is similar to other inflammatory cardiomyopathies (HF, dilated cardiomyopathy [DCM], virus-negative myocarditis) makes myocardial involvement in SSc a really peculiar and complex multifaceted event [19,20,21,22,23,24]
Summary
Heart involvement is frequent and is a major cause of mortality in systemic sclerosis (SSc), being responsible for up to 30% of disease-related deaths [1,2,3]. A recent study indicated that TGF‐b1, a key cytokine in scleroderma, up‐ regulates glycolysis in dermal fibroblasts derived from SSc patients, and inhibition of glycolysis attenuates its pro‐fibrotic effects [59].
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