Salt sensitivity of blood pressure (BP) is associated with higher incidence of cardiovascular disease independent of hypertension; however, it is difficult to diagnose. The paradoxical decrease in BP following high salt intake, which we term “inverse salt sensitivity” also may be associated with increased cardiovascular disease and mortality if sufficient salt intake is not maintained. For these latter individuals, low salt intake will cause an increase in their BP. The most effective method in diagnosing either condition is using an extensive two-week dietary protocol. Finding a simpler method to correctly diagnose these conditions is critical since salt sensitivity affects approximately 25% of the population and inverse salt sensitivity may affect up to 15%. Urinary exosomes provide a unique view of renal metabolic activity and may provide a valuable source for diagnostic biomarkers.

Exosomes are 50–90 nm membrane-derived vesicles found in bodily fluids including blood, saliva, and urine. They encapsulate proteins and mRNA as well as miRNA that may be exchanged as a signaling mechanism between cells. Encapsulated mRNA and miRNA are relatively stable because exosomes protect nucleic acids from extracellular degradation.

miRNAs have been characterized previously in total urine specimens and exosomes from body fluids other than urine, but have yet to be studied in urinary exosomes. Advances have been made in understanding the role of miRNAs in cancer pathogenesis, but less is known about their role in other chronic diseases. Studies have been reported associating certain miRNAs with hypertension but miRNAs have not yet been directly linked to sodium metabolism.

Potentially, miRNAs may be exchanged between tubule segments via exosomes to alter sodium metabolism in various nephron segments.

To characterize the urinary exosome miRNome, researchers at the University of Virginia Health System utilized LC Sciences’ microarray service to explore the miRNA spectrum present within urinary exosomes from ten individuals that had completed our salt sensitivity clinical study. They picked individuals at the two extremes as well as the middle of the continuous variable of salt sensitivity. One group of individuals had a dramatic increase in BP when consuming a high sodium diet, i.e. salt-sensitive. Another group, termed inverse salt-sensitive, had the opposite response to salt, i.e. their BP dramatically dropped while consuming a high sodium diet. These two groups exhibiting extremes of salt sensitivity of BP were compared to a group of normal individuals who fell in the middle of this continuum. These normal control individuals had BP that did not change dependent on sodium consumption, i.e. they were salt-resistant. In the microarray, potential biomarkers were sought based on these three phenotypes. The researchers found that The expression of 45 urinary exosomal miRNAs associates with an individual’s blood pressure response to sodium.

 

Differential miRNA expression in urine exosomes

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Panel A shows the 24 miRNAs that were different between the Salt-Resistant (SR) and Salt-Sensitive (SS) individuals. Panel B shows an additional 21 miRNAs that were different between the Salt-Resistant (SR) and Inverse Salt-Sensitive (ISS) individuals.

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miRNA Microarray Service – LC Sciences provides a miRNA expression profiling service using microarrays based on our in-house developed µParaflo® technology platform. We have standard arrays for all mature miRNAs of all species available in the latest version of the miRBase database (Release 21, July 2014). Our service is comprehensive and includes sample labeling, array hybridization, image data processing and in-depth data analysis. Two-three weeks after receiving your total RNA samples, we’ll send you both the raw and fully analyzed data. [Learn more…]

Reference

Gildea JJ, Carlson JM, Schoeffel CD, Carey RM, Felder RA. (2013) Urinary Exosome miRNome Analysis and its Applications to Salt Sensitivity of Blood Pressure. Clinical Biochemistry 46(12), 1131-4. [article]