Nucleic Acid Aptamer against Renalase to reduce high blood pressure and risk of heart disease

Renalase, a fairly new protein discovered in 2005, is secreted by the kidney (although found in other places like skeletal muscles, heart muscles and liver cells) and enters the bloodstream. This protein degrades catecholamines - hormones secreted by the adrenal gland in response to stress (ex. Norepinephrine, dopamine). By doing so, renalase inadvertently regulates blood pressure by lowering the concentration of catecholamines through degradation. When high levels of catecholamines are present in the bloodstream, renalase concentration levels also increase which is otherwise inactive. However patients with hypertension and kidney problems experienced low levels of renalase causing high concentrations of catecholamines leading to high blood pressure and an increased risk of heart disease.

Although there is already a renalase antibody, a renalase aptamer could be more beneficial in inhibiting its activity and detecting the levels of concentration of renalase. An aptamer is a specific nucleic acid sequence used to bind to a specific target molecule. It has a high specificity and can be selected to bind to any target since it can be obtained via in vitro. In contrast, an antibody requires an animal or a cell culture – making the aptamer more cost effective. Also, an aptamer can be denatured and renatured and still retain its binding ability, whereas an antibody cannot.

Specific aim 1: Selection of RNA aptamers against renalase
There are two reasons that an aptamer for renalase would be important. First off renalase is still a new protein in which further research can be done. Scientists are still proposing whether or not increased levels of renalase leads to kidney failure so by inhibiting the activity of this protein through use of an aptamer, more can be known about its functions. Secondly, a fluorescing aptamer can be beneficial by detecting the levels of renalase in the bloodstream. If levels are low, a dosage of renalase can be injected into the bloodstream which has proven to reduce blood pressure and risks of heart disease.

Abcam sells renalase peptide for $168 - catalog number ab45730.

Sources :
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8029, USA. “Renalase deficiency in chronic kidney disease, and its contribution to hypertension and cardiovascular disease” http://www.ncbi.nlm.nih.gov/pubmed/18277152; accessed Aug. 29, 2011.

Desir GV (May 2009). "Regulation of blood pressure and cardiovascular function by renalase". Kidney Int. 76 (4): 366–70. doi:10.1038/ki.2009.169. PMID 19471322.

Boomsma F, Tipton KF (2007). "Renalase, a catecholamine-metabolising enzyme?". J Neural Transm 114 (6): 775–6. doi:10.1007/s00702-007-0672-1. PMC 2793395. PMID 17385068. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2793395.

Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, Wu Y, Peixoto A, Crowley S, Desir GV (May 2005). "Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure". J. Clin. Invest. 115 (5): 1275–80. doi:10.1172/JCI24066. PMC 1074681. PMID 15841207. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1074681.
^ RNLS renalase, FAD-dependent amine oxidase. Entrez Gene. Accessed July 31, 2009.

Wang J, Qi S, Cheng W, Li L, Wang F, Li YZ, Zhang SP (December 2008). "Identification, expression and tissue distribution of a renalase homologue from mouse". Mol. Biol. Rep. 35 (4): 613–20. doi:10.1007/s11033-007-9131-1. PMID 17846919.

Li G, Xu J, Wang P, Velazquez H, Li Y, Wu Y, Desir GV (March 2008). "Catecholamines regulate the activity, secretion, and synthesis of renalase". Circulation 117 (10): 1277–82. doi:10.1161/CIRCULATIONAHA.107.732032. PMID 18299506. http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18299506.

Ghosh SS, Gehr TWB, Sica DA et al. Effect of renalase inhibition on blood pressure. J Am Soc Nephrology 2006; 17: 208A.

Desir GV, Wu Y, Wang P et al. Renalase deficiency increases sympathetic tone and causes hypertension. J Am Soc Nephrol 2008. Available at http://www.asn-online.org/education_and_meetings/renal_week/archives/

Zhao Q, Fan Z, He J, Chen S, Li H, Zhang P, Wang L, Hu D, Huang J, Qiang B, Gu D (August 2007). "Renalase gene is a novel susceptibility gene for essential hypertension: a two-stage association study in northern Han Chinese population". J. Mol. Med. 85 (8): 877

Desir GV, Li Y, Liu D et al. Downregulation of cardiac renalase expression in CKD, and protective effect of renalase in acute coronary syndrome. J Am Soc Nephrol 2007; 18: 149A.

Here is the link to my manuscript.

Here is my proposal.

Here is progress report #1.