During the course of heart failure pathogenesis, overstimulation with the subsequent downregulation of AGTR1 transcript levels is further enhanced by increased levels of the angiotensin II-generating, angiotensin-converting enzyme (ACE), which is elevated on biopsy specimens of failing human hearts [129,130] and RKIP-transgenic hearts (Figure 5b). The gene discussed is ACE; the disease is heart failure.