Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis

Abstract

Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system. Microarray data sets containing more than 10 normal tissues were downloaded from the GEO database. R software was used to extract expression levels and construct dendrograms of extRAAS genes within each data set. Tissue co-expression modules were then extracted from reproducible gene clusters across data sets. An atlas of the maps of tissue-specific organization of extRAAS was constructed from gene expression and coordination data. Our analysis included 143 data sets containing 4933 samples representing 23 different tissues. Expression data provided an insight on the favored pathways in a given tissue. Gene coordination indicated the existence of tissue-specific modules organized or not around conserved core groups of transcripts. The atlas of tissue-specific organization of extRAAS will help better understand tissue-specific effects of RAAS. This will provide a frame for developing more effective and selective pharmaceuticals targeting extRAAS.

Periarterial fat from two human vascular beds is not a source of aldosterone to promote vasoconstriction

“…Likewise, no aldosterone was detected in PRAT and abdominal adipose tissue conditioned medium despite prolonged incubation. This contrasts with findings from previous studies where aldosterone synthase and aldosterone release were detected in mouse epididymal primary adipose tissue and in cultured mouse 3T3-L1 adipocyte cells as well as human subcutaneous and abdominal primary adipose tissue (8,45,46). Especially, the lack of general aldosterone synthase expression across samples of abdominal adipose tissue contrasts with earlier findings (8,45).…”

“…MR-dependent aldosterone-induced endothelial dysfunction is also found in humans in vivo [summarized by Lyngsø et al (38)], but the coupling with vascular MR has not been established. A paradoxical observation is that the beneficial effect of MRA is often observed in the absence of elevated systemic aldosterone levels (50 -52), and therefore either local sources of the hormone (8,45) or illicit glucocorticoid-mediated MR activation (21) must be considered. Most arteries are surrounded by perivascular adipose tissue (PVAT; 28).…”

“…Moreover, murine primary adipocytes may synthesize and secrete aldosterone (8,46). The mouse 3T3-L1 adipocyte cell line, mouse epididymal and human abdominal and gluteal primary adipocytes all express aldosterone synthase (CYP11B2) and secrete aldosterone (8,45). ANG II type 1 receptor blockade reduces aldosterone release from db/db adipocytes, which suggests ANG II dependency of aldosterone synthase.…”

Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds

“…This local tRAS is present in nearly all organs and tissues of the body including heart, lungs, kidneys, liver and has also been described in the skin [7]. The local functions of tRAS in different tissues have been described by Paul et al [8].…”

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“…In our study, a decrease in AT1R mRNA observed in the atheroma plaque could thus be indicative of a local increase in angiotensin II. Although the mechanisms of the increased mRNA levels observed in this study have not yet been characterized, the modulation of tissue angiotensin system gene transcription in the arterial wall in atheroma provides a molecular explanation for the benefit of ACE inhibitors [22][23][24] .…”