Congestive heart failure is the leading cause of cardiovascular disease and related death, and is associated with elevated levels of angiotensin II in the blood (which causes vessel contraction and high blood pressure) in addition to muscle wasting. Although this weight loss is an important predictor of poor outcome in heart failure, the mechanisms underlying this association are poorly understood. Previous studies in rats by Patrick Delafontaine and colleagues from Tulane Medical University Center showed that administration of angiotensin II causes a marked reduction in body weight accompanied by a decrease in the levels of insulin-like growth factor-1 (IGF-1) in both the blood and skeletal muscle. This suggested that decreased expression of IGF-1 could help mediate the wasting effect of angiotensin II.

In their most recent study appearing in the Journal of Clinical Investigation, these same authors used a variety of techniques to demonstrate that angiotensin II inhibits IGF-1 signaling in skeletal muscle and that this effect is causally related to skeletal muscle loss. They also demonstrate that in mice genetically engineered to overproduce IGF-1 there is a complete reversal of angiotensin-induced weight loss. The authors provide strong evidence that the signaling pathway known as the Akt/mTOR/p70S6 kinase pathway is involved in this ability of IGF-1 to prevent muscle loss.

These findings have broad relevance to the events leading to muscle loss in a variety of conditions such as chronic congestive heart failure and chronic renal failure. In addition, the study provides a strong rationale for developing strategies to activate the skeletal muscle IGF-1 system in wasting conditions for therapeutic benefit.

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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
13-Jan-2005

Page: 1
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