Serial killer: angiotensin drives cardiac hypertrophy via TGF-β1

How a seemingly simple signal -work load -becomes transduced into longterm structural, functional, and molecular responses that sustain or impair the performance of the heart is the defining enigma in cardiac hypertrophy (1, 2).Much is now known of this ensemble of responses, which encompass dozens if not hundreds of changes in cardiac gene expression, including sarcomeric proteins, ion pumps and channels, enzymes, and peptide growth factors and cytokines.These last, soluble, factors provide opportunity for both feedback and feed-forward relationships and are attractive, conceptually, as at least a partial explanation of the hypertrophic phenotype.First, growth factor signaling cascades are better understood in fundamental terms than is mechanical signal transduction, especially given the present lack of clarity as to how and where load is sensed in the heart.Second, secreted signals provide an intuitively plausible explanation for the cross-talk among cardiac myocytes, fibroblasts, and the vasculature.Third, secreted signals provide a readily exploited site for therapeutic intervention: interfering with ligand-receptor interaction.