Urinary Exosome miRNome Analysis and its Applications to Salt Sensitivity of Blood Pressure

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 hypertensio 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 investigate microRNAs (miRNAs) in urinary exosomes and their association with an individual’s blood pressure response to dietary salt intake, the human urinary exosomal miRNome was examined by microarray.

Of 1898 probes tested, 194 miRNAs were found in all subjects tested. 45 miRNAs had significant associations with salt sensitivity or inverse salt sensitivity. The expression of 45 urinary exosomal miRNAs associates with an individual’s blood pressure response to sodium.

  • Gildea JJ, Carlson JM, Schoeffel CD, Carey RM, Felder RA. (2013) Urinary Exosome miRNome Analysis and its Applications to Salt Sensitivity of Blood Pressure. Clin Biochem  [Epub ahead of print]. [abstract]

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