The Molecular Mechanism of Diastolic Heart Failure

Abstract

Diastolic heart failure (DHF) is a group of clinical syndromes related to the performance of the pulmonary circulation and systemic circulation, with normal left ventricular (LV) systolic function. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling, and/or increased stiffness. These conditions result in impaired LV diastolic relaxation ability and a decrease in myocardial compliance. In recent years, studies on the mechanisms of DHF have focused on the renin-angiotensin-aldosterone system, inflammatory cytokines, oxidative stress, the process of myocardial calcium cycling, and associated proteins. The pathomechanism has been proven to be due to a deficiency in ATP, and Ca²⁺ cannot be reduced by sarcoplasmic reticulum calcium pump (SERCA2a), which leads to myocardial diastolic dysfunction. The correlation between the degradation process of ATP and its metabolites and DHF has also been studied in recent years. This paper summarizes the views on the above and analyzes the correlations between the molecular mechanisms.

Cenário Disfuncional dos Principais Componentes Responsáveis pelo Equilíbrio do Trânsito de Cálcio Miocárdico na Insuficiência Cardíaca Induzida por Estenose Aórtica

“…[36][37][38] Porém, a ativação não harmônica desses microssistemas devido às demandas cardíacas e corporais gera diversas respostas fisiopatológicas, incluindo danos ao manejo do cálcio dos cardiomiócitos. 1,[34][35][36][37][38][39][40][41][42] A i n c o m p a t i b i l i d a d e d o C a 2 + c i t o s ó l i c o e m cardiomiócitos é um dos mecanismos chave para o mal funcionamento do coração em resposta a vários tipos de lesão. 1,4,39 Em modelos de IC, incluindo a estenose aórtica experimental, pesquisadores caracterizaram mudanças na expressão e função transmembrana, assim como proteínas intracelulares que regulam o trânsito de cálcio.…”

Biomarkers of Inflammation in Left Ventricular Diastolic Dysfunction

“…On the other hand, extracellular matrix (ECM) proteins such as MMP can act as IF stimuli by modulating the proinflammatory response of the heart, synthetizing cytokines and growth factors. In patients with myocardial injuries such as ischemia, myocarditis, and advanced heart failure, tenascin-C (Tn-C), an ECM glycoprotein, was transiently expressed in myocardial tissue, in association with immediate tissue repair response and the final deposit of collagen in the damaged tissue [17].…”

Inflammation‐induced left ventricular fibrosis is partially mediated by tumor necrosis factor‐α

“…Several factors including increased collagen volume, collagen cross‐linking, and disruption of collagen turnover contribute to the formation of a stiffened extracellular matrix (El Hajj et al, 2017). Inflammation modulates the mechanisms of extracellular matrix remodeling and may thus contribute to the development of diastolic dysfunction (Goldsmith et al, 2013; Gu et al, 2015). Increased expression of pro‐inflammatory cytokines has been associated with accelerated collagen formation (Porter & Turner, 2009), increased collagen cross‐linking (Suthahar et al, 2017), and altered collagen degradation, which ultimately lead to dysregulation of collagen turnover and LV fibrosis (Li et al, 2000).…”