Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease

Abstract

For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions “Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?” and “Could Se be recommended as a therapeutic strategy for CCC?”, we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-β as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-β pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.

Pirfenidone Prevents the Onset of Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy

“…Early treatment of infected mice with verapamil promoted a reduction in inflammation and fibrosis in the acute phase of Chagas disease, while late treatment did not result in a beneficial effect [59]. Fibrosis in the heart is mediated at least partially by TGF-β, an important biomarker for the genesis of cardiac fibrosis in Chagas disease [16,60]. Additional inhibitors of TGFβ pathway have been examined in experimental T. cruzi infection in vivo.…”

The Saga of Selenium Treatment Investigation in Chagas Disease Cardiopathy: Translational Research in a Neglected Tropical Disease in Brazil

“…About 20-30% of the infected persons will develop chronic complications related to cardiovascular and digestive systems, and CCC is the most relevant infectious heart condition in Latin America [6,9,10]. We recently reviewed the complex physiopathology of CCC and the possible interactions where Se could act to reduce oxidative damage that is caused by multiple determinants [11,12]. Figure 1 shows the main strategies that we could mobilize to face the complex physiopathogenesis of CD, which involves anti-parasite drugs (AP), modulators of inflammation (MI), immune stimulators (IS), regulators of pathology (RP), and the combination of different therapeutic strategies (CT).…”

Clinical trials for Chagas disease: etiological and pathophysiological treatment

“…Furthermore, 10% can present megacolon or megaesophagus, representing the digestive form (DCD). CCC has several pathological characteristics, such as thinning of the ventricular wall, changes in the size and shape of the heart, heart failure, atrophy with loss of myocardial fibers and the presence of dense and fibrous scar tissue (Bonney and Engman, 2008;Araujo-Jorge et al, 2022a). Cardiac manifestations of CD include abnormalities of the intraventricular conduction system, bradycardia, ventricular arrhythmias, sinus node dysfunction, heart failure, left ventricular aneurysms, and enlargement and dysfunction of the heart.…”