MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium

Bibliographic Details
Main Author:	Pandey, Raghav
Language:	English
Published:	University of Cincinnati / OhioLINK 2017
Subjects:	Biology Cardiomyocytes Cardiac regeneration microRNAs Heart disease Cardiovascular Cardiovascular diseases
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505124343198575

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-ucin15051243431985752021-08-03T07:04:08Z MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium Pandey, Raghav Biology Cardiomyocytes Cardiac regeneration microRNAs Heart disease Cardiovascular Cardiovascular diseases Cardiovascular diseases have been the biggest killer in the United States for decades. Despite tremendous research and new innovations, these trends do not seem to be slowing down, with more than 1 in every 3 deaths related to cardiovascular disease in 2016. In the U.S. cardiovascular diseases affect close to 92.1 million people, causing 807,775 deaths each year. According to the American Heart Association statistics report update of 2016, 17.3 million deaths worldwide were attributed to cardiovascular diseases. Moreover, this number is estimated to rise to more than 23.6 million by the year 2030. In addition, U.S. healthcare cost associated with cardiovascular disease has been rising with a massive $316 billion of associated direct and indirect cost, which is estimated to rise to $918 billion by the year 2030. Moreover, as the average age of the U.S. population increases this trend will most likely stay the same, if not increase. Etiologically, lack of oxygen and blood to the heart tissue is one the major cause of this ischemic injury and scar formation. This happens through the buildup of plaque in the arteries which reduces the blood flow and when left untreated can shut down the blood supply to downstream tissue. Our current medical approaches to deal with ischemic injuries include blood thinners, stents, beta-blockers, and surgical cleaning of the plaque. Although, heart transplants are the most optimal treatment, unavailability of donor hearts still remains a major concern when dealing with this problem. While microRNAs were first discovered in early 1990s by Ambros in C. elegans it was not until mid-2000s that first cardiac microRNA was discovered and studied. Binding to the 3’UTR (untranslated region) and inhibiting expression of the gene is the canonical mode of action for microRNAs, however there have been reports of 5’UTR binding and other non-canonical modes of action. Recent work by Matkovich et al. 2013 even determined miRNAs regulating other cardiac miRNAs. In addition to their discovery, microRNAs were shown to be differentially regulated in diseased and non-diseased cases. In addition, work by Eulalio et al. 2012 was one of the first to show miRNAs inducing proliferation in cardiomyocytes and inducing regeneration of lost myocardium, post injury. In this work, we have furthered the understanding of miRNAs and cardiovascular disease (specifically myocardial infarction) by showing a significant proliferation in adult cardiomyocytes both ex-vivo and in-vivo, which reduces infarction size and improves heart function as early as one month post treatment. We also confirmed the effect across different species (mice, rats, and human) and showed that miR1825 can induce significant proliferation in all three species. Lastly, we project a very high translational potential for this work due to the nature of miRNAs as a therapeutic: readily available, longer shelf-life, and no prerequisite for an autologous donor. 2017-12-15 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505124343198575 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505124343198575 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Biology Cardiomyocytes Cardiac regeneration microRNAs Heart disease Cardiovascular Cardiovascular diseases
spellingShingle	Biology Cardiomyocytes Cardiac regeneration microRNAs Heart disease Cardiovascular Cardiovascular diseases Pandey, Raghav MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
author	Pandey, Raghav
author_facet	Pandey, Raghav
author_sort	Pandey, Raghav
title	MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
title_short	MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
title_full	MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
title_fullStr	MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
title_full_unstemmed	MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium
title_sort	microrna mediated proliferation of adult cardiomyocytes to regenerate ischemic myocardium
publisher	University of Cincinnati / OhioLINK
publishDate	2017
url	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505124343198575
work_keys_str_mv	AT pandeyraghav micrornamediatedproliferationofadultcardiomyocytestoregenerateischemicmyocardium
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MicroRNA Mediated Proliferation of Adult Cardiomyocytes to Regenerate Ischemic Myocardium

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