Skeletal muscle inflammation and atrophy in heart failure

Abstract

Heart failure represents a systemic disease with profound effects on multiple peripheral tissues including skeletal muscle. Within the context of heart failure, perturbations in skeletal muscle physiology, structure, and function strongly contribute to exercise intolerance and the morbidity of this devastating disease. There is growing evidence that chronic heart failure imparts specific pathological changes within skeletal muscle beds resulting in muscle dysfunction and tissue atrophy. Mechanistically, systemic and local inflammatory responses drive critical aspects of this pathology. In this review, we will discuss pathological mechanisms that drive skeletal muscle inflammation and highlight emerging roles for distinct innate immune subsets that reside within damage muscle tissue focusing on the recently described embryonic and monocyte-derived macrophage lineages. Within this context, we will discuss the how immune mechanisms can be differentially targeted to stimulate skeletal muscle inflammation, catabolism, fiber atrophy, and regeneration.

Current Studies and Future Directions of Exercise Therapy for Muscle Atrophy Induced by Heart Failure

“…Heart failure can increase inflammation, cause lower protein synthesis than degradation, reduce mitochondrial function, increase reactive oxygen species (ROS), change hormone content such as angiotensin II (AngII) and insulin like growth factor 1 (IGF-1), thus leading to muscle atrophy (31). Here, we present that exercise can reverse the adverse pathways caused by heart failure, so as to alleviate muscle atrophy (Figure 2).…”

“…Chronic inflammation is one of the characteristics of muscle atrophy induced by heart failure (31). Exercise decreases the secretion of inflammatory factors such as TNF-α, IL-6, and Creactive protein (CRP), which can directly reduce the process of protein hydrolysis and catabolism, reduce the degree of muscle loss, so as to achieve the anti-inflammatory effect of exercise (32,33).…”

Heme-Induced Oxidation of Cysteine Groups of Myofilament Proteins Leads to Contractile Dysfunction of Permeabilized Human Skeletal Muscle Fibres

“…However, the molecular pathophysiology of skeletal muscle myopathy is not well understood. This pathology is characterized by multiple alterations, like mitochondrial dysfunction, systemic inflammation, oxidative stress, and decreased muscle strength (isometric force), and atrophy of oxidative fibres [31]. It was shown that heart failure also induces skeletal muscle myopathy, and free heme was detected in patients with chronic heart failure [32], thus implicating a potential cause for the mechanical impairment of the myocardium [19].…”

Transcriptome analysis of skeletal muscles revealed the effect of exercise on the molecular mechanisms regulating muscle growth and metabolism in patients with heart failure

“…Кроме того, известно, что дифференциально экспрессируемый ген CYR61, относящийся к группе белков, связывающих инсулиноподобный фактор роста (IGF) (табл. 2), участвует в регуляции ангиогенного фактора VEGF через механизмы цитоскелетной механотрансдукции [20], а увеличение его экспрессии в скелетных мышцах как на уровне мРНК, так и на уровне белка было обнаружено у здоровых людей после физической нагрузки. Кроме того, было показано, что сывороточный уровень CYR61 коррелирует со смертностью в течение 6 мес.…”