关键词：
HEART failure
RESEARCH
MUSCLE cells
PROTEINS -- Research
CARDIAC contraction -- Regulation
TISSUES
摘要：
New Findings center dot What is the topic of this review? Heart failure is a progressive disease syndrome that, in the early stages, involves subtle tissue and cellullar changes. This review highlights novel imaging techniques that allow quantitative investigation of the underlying pathophysiological mechanisms in vivo. center dot What advances does it highlight? High-content voltage imaging of the left ventricle showed significant conduction slowing in the mdx mouse model of heart failure, corresponding to selective loss of Na+ channels and dystrophin in the lateral cardiac myocyte membrane. Super-resolution STED imaging after myocardial infarction uncovered proliferative, differential remodelling of individual T-tubules and network properties leading to intracellular Ca2+ release heterogeneity. These techniques reveal potential mechanisms of arrhythmia susceptibility, tissue degeneration and contractile dysfunction. Heart failure (HF) is a complex disease syndrome, which affects physiology at all levels, from the molecule to the whole organism. Following a causative insult, a maladaptive response occurs, which sustains cardiac remodelling and leads to a final common pathway of debilitating HF symptoms. In terms of mechanisms, distinct defects of excitationcontraction coupling compartments and organelles have been identified in cardiac samples of patients and animal models, which include changes in Ca2+ transport proteins and T-tubules. From a physiological standpoint, the source of regulatory intracellular Ca2+ is defined by approximate to 20,000 Ca2+ release units per cardiac myocyte, which jointly modulate contractile force production. We and others have characterized key changes in protein and membrane components of Ca2+ release units during HF in patient samples and transgenic models to gain insight into complex disease mechanisms. While earlier HF studies identified intracellular Ca2+ release as a major cause of contractile dysfunction, electrical dysfunction
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中文科技期刊
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