Systems Biology Applied to Heart Failure With Normal Ejection Fraction

Abstract

Heart failure with normal ejection fraction (HFNEF) is currently the most prevalent clinical phenotype of heart failure. However, the treatments available have shown no reduction in mortality so far. Advances in the omics sciences and techniques of high data processing used in molecular biology have enabled the development of an integrating approach to HFNEF based on systems biology.This study aimed at presenting a systems-biology-based HFNEF model using the bottom-up and top-down approaches.A literature search was conducted for studies published between 1991 and 2013 regarding HFNEF pathophysiology, its biomarkers and systems biology. A conceptual model was developed using bottom-up and top-down approaches of systems biology.The use of systems-biology approaches for HFNEF, a complex clinical syndrome, can be useful to better understand its pathophysiology and to discover new therapeutic targets.

Amyloidosis: Systems-Based Therapies

“…Tafamidis is an agent that exhibits its therapeutic effect by stabilizing the TTR protein, thus preventing its misfolding and subsequent deposition in organs of the body. In a randomized, placebo-controlled, double blind study performed in September 2018, Tafamidis was found to improve the quality of life of amyloidosis patients by slowing the progression of the disease and reducing the functional impairment of affected nerves and systems throughout the body [58,59]. Other drugs that also may be beneficial in TTR amyloidosis cases include an NSAID called Diflunisal, doxycycline, and an antisense therapy called ISIS-TTRrx.…”

“…ISIS-TTRrx's mechanism of action differs and works by directly DOI: http://dx.doi.org /10.5772/intechopen.85201 suppressing the gene that expresses the TTR protein. These agents are still being investigated for efficacy in experiments and clinical trials [59].…”

Study of comparative proteome between normal and inverted karyotypes of human mesenchymal stem cells

“…Systems biology is a tool used to build protein-protein interaction networks in order to understand the interactions between these molecules. Systems biology enables constructing mathematical models, simulations, data processing techniques, and integrating information, thereby achieving a better understanding of the interactions between the living systems components and their biological processes (Mesquita, Jorge, Souza Junior, & Cassino, 2014). Therefore, systems biology was used in order to analyze the paracentric inversion in MSC-UCh at a protein level.…”

Modulação promovida pelo peptídeo natriurético tipo C sobre a resposta contrátil induzida pela fenilefrina em aorta torácica e artéria mesentérica de resistência isoladas de ratos submetidos ao choque séptico

“…Alterações na matriz extracelular com o aumento do depósito de produtos finais de glicação avançada, bem como alteração do perfil do colágeno, apoptose, rigidez e hipertrofia do cardiomiócito foram demonstradas no remodelamento concêntrico, mesmo na ausência da hipertrofia do VE na ICFEN (Borbély et al, 2009;Roscani;Matsubara, Matsubara, 2010;Mesquita et al, 2014). Além disso, a anormalidade do relaxamento e o aumento da rigidez ventricular levam ao aumento das pressões de enchimento do VE, que são marcadores da presença de disfunção diastólica.…”

“…Além disso, a anormalidade do relaxamento e o aumento da rigidez ventricular levam ao aumento das pressões de enchimento do VE, que são marcadores da presença de disfunção diastólica. Alterações na rigidez arterial e na função endotelial estão presentes nos pacientes portadores de ICFEN, contribuindo para o agravamento da disfunção diastólica, com aumento da pós-carga e acarretando ou intensificando a isquemia miocárdica (Borbély et al, 2009;Roscani;Matsubara, Matsubara, 2010;Mesquita et al, 2014). Desta forma, as alterações observadas no sistema vascular, como menor resposta contrátil à PE e modulação negativa induzida pelo CNP mais pronunciada em ratos CLP, podem estar relacionadas às alterações cardíacas observadas nos ratos CLP.…”