Expression of a transcript encoding for cytosolic renin in the diseased human heart

Abstract

2Secretory renin promotes hypertrophy, apoptosis, necrosis and fibrosis through angiotensin 3 generation. It has been claimed that local expression of renin contributes to the deleterious 4 effects of the renin-angiotensin system in the heart. Besides the classic renin transcript (renin-5 a), encoding for secretory renin, a putative brain-specific (renin-b) and a putative lung-6 specific (renin-c) transcript may exist in human. In contrast to secretory renin, renin-b cannot 7 be secreted, remains within the cytosol and is imported into mitochondria. In contradiction to 8 renin-a, renin-b exerts cardioprotective effects in hearts and in cardiac cells of the rat under 9 ischemia related conditions. To date, available data on cardiac renin expression remain 10 inconsistent. Nobody has yet investigated which renin transcripts are expressed in the human 11 heart. We systematically analyzed the levels of renin transcripts using specific and sensitive 12 nested reverse-transcriptase polymerase chain reactions (RT-PCR) in human ventricular 13 biopsies obtained from patients with heart diseases. In the 33 biopsies available, neither the 14 expression of classic renin-a, nor of the alternative renin-c was detected. In contrast, the renin-15 b transcript, which was previously classified as brain-specific, was found in 11/33 ventricular 16 biopsies. Our data exclude the expression of secretory renin and indicate that local expression 17 of cytosolic renin but not of secretory renin can play a functional role in the human heart. 18 19 20