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An intriguing role of circular RNA in insulin resistance and endothelial dysfunction: the future perspectives

Hypertension Research volume 45, pages 1843–1845 (2022)Cite this article

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are the leading causes of death worldwide, and obesity, aberrant lipid profiles, endothelial dysfunction, and insulin resistance are the most common causes. In T2DM, CVDs are the major cause of morbidity and mortality; these diseases are exacerbated by hypertension because they share common risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodeling, atherosclerosis, dyslipidemia, and obesity. Insulin, as a major hormone in cell metabolism, regulates glucose uptake and oxidation and glycogen formation and suppresses lipid oxidation. This hormone also plays a role in blood pressure regulation by controlling glucose and lipid metabolism, the renin–angiotensin–aldosterone system, oxidative stress, inflammation, and immune system activation, which may reflect its role in diabetes and endothelial dysfunction [1]. T2DM and CVDs are produced by major alterations in these signaling proteins and their activity and result in hyperglycemia and the activation of reactive oxygen species, which leads to metabolic inflexibility, vascular inflammation, endothelial dysfunction, and insulin resistance. In this sense, genetic and epigenetic factors will continue to gain importance in relation to metabolic disorders and the metabolic imbalance.

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs produced through back splicing/noncanonical splicing processes. circRNAs are three times longer than linear RNAs and have covalent bonds that make them very stable [2, 3]. Its complementary Alu repeats help promote and maintain its circular structure. circRNAs are free of polyadenylation tails due to their tightly looped structure with no 5′ and 3′ end structures that resist nuclease activity, such as polyA tails and 5′ caps. As a result of their nature, these RNAs are currently being investigated as diagnostic and therapeutic targets. circRNAs have been understudied for a long time, and their regulatory potential remains under investigation. They were formerly assumed to be rare isoforms caused by splicing errors. However, with technological advancements in computational and high-throughput screening, it is now well documented that circRNAs are extensively expressed and substantially conserved across species. It is now established that circRNAs behave as sponges for microRNA, allowing upregulation of target mRNA. In recent decades, circRNA detection and characterization approaches have steadily revealed their biological properties, which include cellular abundance, diversity, evolutionarily conserved, cell selective expression, and their role across tissues. circRNAs are expressed in specific patterns in tissues, exosomes, blood, and saliva. Importantly, the strategies for the detection of circRNAs in biological systems are easier than the methods for protein detection [4, 5]. Due to the ease of their detection, circRNAs are regarded as biomarkers for diseases including cancer, hypertension [2], and T2DM and its complications. CircRNAs are critical insulin resistance regulators and play a role in the development of metabolism-related disorders such as T2DM and CVDs.

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Acknowledgements

The financial support provided by the Department of Science and Technology- Science and Engineering Research Board (DST-SERB) under the Engineering Research Council (Funding Approval No: EEQ/2019/000568), Government of India, to Dr Selvaraj Jayaraman is gratefully acknowledged.

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  1. Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India

    Monisha Prasad, Selvaraj Jayaraman & Vishnu Priya Veeraraghavan

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Correspondence to Selvaraj Jayaraman.

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Prasad, M., Jayaraman, S. & Veeraraghavan, V.P. An intriguing role of circular RNA in insulin resistance and endothelial dysfunction: the future perspectives. Hypertens Res 45, 1843–1845 (2022). https://doi.org/10.1038/s41440-022-01006-y

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