Inhibition of Aortic Medial Calcification: miPEP-200b and miRNA-200b as Potential Mediators Volume 2 - Issue 5

Sepehr Saberian, Sharif Morsalin, Jinbo Fang, Veena N Rao and E Shyam P Reddy*

• Cancer Biology Program, Department of OB/GYN, Morehouse School of Medicine, USA

Received:August 04, 2021;   Published:August 16, 2021

Corresponding author: E Shyam P Reddy, Professor and Director, GCC Distinguished Cancer Scholar, Cancer Biology Program, Department of OB/GYN, Morehouse School of Medicine, Atlanta, GA, USA

DOI: 10.32474/LOJPCR.2021.02.000147

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Abstract

When considering the flow of genetic information in a cell, the traditional pathway of DNA to RNA to protein is what first comes to mind. In recent years, it has been clearly demonstrated that this pathway must be revised from new data and discoveries. The extensive study of noncoding RNA (ncRNA) has led to the discovery of many of its functions that were once unknown. Perhaps even more intriguing is our recent discovery that was made in an already new field of study. We demonstrated that primary microRNA-200a (pri-miRNA-200a) and pri-miRNA-200b possess open reading frames (ORF) that were recognized by ribosomes, allowing the pri-miRNAs to be translated into two peptides, miPEP-200a and miPEP-200b. Furthermore, studies have shown that these peptides are involved in the inhibition of cell migration in breast and prostate cancer cells and may even serve as significant prognostic markers of clinical outcomes. We have previously shown that miPEPs have downstream functional effects very similar to their miRNA counterparts, resembling many other protective mechanisms observed in nature. This “double-edged functional sword” allows for continued activity despite decreased functionality in one part of the system. Although the anti-neoplastic role of these peptides has recently been an area of interest, not much research has been published regarding their role in cardiovascular disease. In one study, it was demonstrated that a single nucleotide polymorphism in the gene coding for miRNA-200b might result in increased protein kinase A (PKA) activity that ultimately leads to activation of thrombocytes and ensuing atherosclerosis. PKA is not only involved in platelet activity but is rather known to play a role in a multitude of cellular pathways. Of interest is PKA’s involvement in medial aortic calcification, a process that has been implicated in isolated systolic hypertension (ISH); this condition is associated with increasing age. We hypothesize that in the same way that miRNA-200b plays a role in decreasing PKA activity in atherosclerotic processes, the peptide miPEP-200b may also act as an inhibitor of PKA-induced aortic medial calcification. If this association is shown to be present, focused therapy with miPEP-200b and miRNA-200b, along with PKA inhibitors, may significantly reduce the incidence, as well as prevalence, of isolated systolic hypertension in older age groups, leading to a decreased incidence of diastolic heart failure secondary to longstanding hypertension.

Abstract| Introduction| Mirna and Mipep Interaction| PKA and Aortic Calcification| Aortic Calcification, Hypertension, and Heart Failure| Discussion| Conclusion| Acknowledgement| References|