Exosomal non-coding RNA exhibit sex-specific profiles in salt sensitive hypertension

Exosomes are secreted by various living cells and can be found in all body fluids, especially in cerebrospinal fluid (CSF) and plasma, thereby providing a source of biomarkers for cardiovascular diseases that can be used for patients’ diagnostic. Using high-throughput sequencing technologies, exosomes have been found to contain different RNA populations particularly non-coding RNA. Recently, many non-coding RNA have been recognized as key regulators in the progression of hypertension. In this study we hypothesized that female and male C57BI/6J mice exhibit different microRNA (miR) profiles after deoxycorticosterone acetate (DOCA)+salt hypertension treatment. CSF (10 μl) and plasma (100 μl) were collected from 3-month-old mice and again after 3 weeks of DOCA-salt treatment before exosomes isolation and processing for high throughput small RNA sequencing (Creative Biolabs). Analysis was performed using R language and RStudio ( https://rstudio.com/ ) as an integrated development environment. Global miRNA analysis of CSF exosomes shows different expression miRNA profiles in DOCA+salt male mice compared with their own baseline values. In addition, we observed a remarkable difference in global miRNA expression profile between DOCA+salt male mice and DOCA+salt females (p-value < 2.2e-16), while no significant difference was detected between DOCA+salt females and their baseline values (p-value = 0.6679). Moreover, we observed that there are three clusters of around 200 miR that have different expression levels in DOCA+salt males. Our analysis identified around 74 upregulated miRNA in DOCA+salt males compared to DOCA+salt females. The maximum level of expression belonged to the muscle-specific miRNA (myomiR) miR-1a-3p, miR-206-3p and miR-26a-5p which were highly accumulated in CSF derived exosomes. These top three upregulated miRNA were associated with 282 validated target genes among which, two pivotal genes, ACE2 and ADAM17, were identified in the PPI network, miRTargetLink, and by KEGG analysis. miR-26a-5p was mostly associated with ACE2 and ADAM17 and the mRNA expression of ADAM17 was associated with reduced miR-206-3p. In conclusion, our bioinformatic analysis identified three miRNA and associated them with two key molecules involved in salt sensitive hypertension. Further analysis is likely to highlight more diagnostic biomarkers and potential candidates for the development of new therapeutic approaches. This work was supported in part by a research grant from the National Institutes of Health (HL163588). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.