The apelin and AT1 receptors are co-expressed throughout the cardiovascular system, and the apelin system opposes the actions of the renin-angiotensin system (Figure 3).10,37,51 The systems may also reciprocally regulate each other.52 In an animal model of heart failure, down-regulation of cardiac apelin and apelin receptor mRNA is restored by AT1 blockade. The gene discussed is APLN; the disease is heart failure.