Angiotensin II as candidate of cardiac cachexia

Purpose of review Congestive heart failure is increasing in prevalence and represents a major public health problem. The syndrome of advanced heart failure often includes muscle wasting, commonly termed cardiac cachexia, which is predictor of poor outcome. Mechanisms of cardiac cachexia are poorly understood, but there is recent evidence that increased angiotensin II, interacting with the insulin-like growth factor-1 system, plays an important role. Recent findings In animals, angiotensin II produces weight loss through a pressor-independent mechanism, accompanied by decreased levels of circulating and skeletal muscle insulin-like growth factor-1 and increased mRNA levels of the ubiquitin ligases atrogin-1 and Muscle RING finger-1 in skeletal muscle. Reduced insulin-like growth factor-1 action in muscle leads to increased proteolysis, through the ubiquitin-proteasome pathway, and increased apoptosis. These changes are blocked by muscle-specific expression of insulin-like growth factor-1, likely to be via the Akt/mTOR/p70S6K signaling pathway. Summary The link between insulin-like growth factor-1, the ubiquitin-proteasome pathway, and angiotensin II effects has widespread clinical implications for the understanding of mechanisms of catabolic conditions. Therapeutic interventions targeting cross-talk mechanisms between angiotensin II and insulin-like growth factor-1 effects could provide new approaches for the treatment of muscle wasting.