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Kamalben B. Prajapati

Abstract

Introduction: Cardiovascular diseases (CVD) are responsible for millions of deaths worldwide every year and remain one of the main causes of death in low- middle-income countries. Current methods of treating CVD involve the use of lipid-lowering drugs although these patients continue to suffer from atherosclerotic disease risk. Novel RNA therapeutic strategies are being brought to light with the advancement in our understanding of cellular mechanisms and communication, however, these need to be evaluated critically before their clinical use. 


Methods: Electronic literature databases such as PubMed and Google Scholar were used to access review papers and research studies done in the past 25 years. Studies most relevant to RNA cardiovascular therapeutics were used to study therapeutic interventions and their limitations.


Results: MicroRNAs (miRNAs), a subset of non-coding RNAs play an important function in cell-cell communication and microenvironment remodeling due to their role in cellular processes such as differentiation, proliferation, and apoptosis. Dysregulation of miRNA synthesis has been shown to drive disease pathology.  Administration of the miRNAs downregulated during disease or silencing the activity of pathogenic miRNA can be used to establish the genetic composition of a healthy individual. Exosomes are cell-derived bilipid layer extracellular vesicles, 40-150 nm in size, which conduct paracrine signaling by carrying a cargo of mRNAs, non-coding RNAs, and proteins. They could be used as an efficient delivery method for miRNAs. Gene silencing therapies targeting the ApoCIII gene have emerged as novel therapeutic interventions to treating CVD with genome-wide association studies demonstrating enhanced cardioprotective function with ApoCIII deficiency. Gene silencing through miRNA delivery and antisense oligonucleotides reveals new avenues of CVD treatment.


Discussion: Novel therapeutics addressing miRNA dysregulation and gene expression regulation come with caveats that need to be addressed before they are prescribed. This review describes the role of the gene silencing interventions and the implementation barriers that delay their approval for use in treating heart disease.


Conclusion: The treatments and limitations addressed in this review suggest more studies are needed to determine the pharmacokinetic aspects of RNA drugs prior to establishing the use of RNA therapeutics along with conventional cholesterol-lowering drugs to ameliorate CVD risk.

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Section
Review