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Making Sense in Antisense: Therapeutic Potential of Noncoding RNAs in Diabetes-Induced Vascular Dysfunction

DOI: 10.1155/2013/834727

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Abstract:

The rapid rise of type II diabetes mellitus and its accompanying vascular complications call for novel approaches in unravelling its pathophysiological mechanisms and designing new treatment modalities. Noncoding RNAs represent a class of previously unknown molecular modulators of this disease. The most important features of diabetes-induced vascular disease, which include metabolic deregulation, increased oxidative stress, release of inflammatory mediators like adipokines, and pathologic changes in vascular cells, all are depicted and governed by a certain set of noncoding RNAs. While these mechanisms are being unravelled, new diagnostic and therapeutic opportunities to treat diabetes-induced vascular disease emerge. 1. Prevalence of Diabetes and Vascular Complications The prevalence of type II diabetes mellitus (T2DM) and related metabolic syndrome keeps rising at an alarming rate and becomes a global health issue affecting children, adolescents, and adults. According to the World Health Organization, approximately 346 million people worldwide have T2DM, and this number is estimated to almost double by 2030 [1, 2]. T2DM is a progressive multisystem disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality [3]. Patients with diabetes and/or metabolic syndrome have a significantly increased risk of cardiovascular complications compared to people with normal insulin sensitivity and production. In the past years, many studies have tried to reveal the mechanisms for diabetic vascular complications, with varying degrees of success. The recent discovery of noncoding RNA (ncRNAs, e.g., microRNAs and long noncoding RNAs), as well as their influence on human pathophysiology, provides us with new opportunities to unravel and positively influence the disease process. In the present review, we summarize the pathophysiology of T2DM associated vascular disease and highlight the association of ncRNA with diabetic vascular dysfunction. 2. Pathophysiology of Diabetic Vascular Disease The complications of T2DM encompass a diverse range of pathologies of large and small arteries, leading to diabetic macrovascular occlusive disease and/or microvascular dysfunction, which include coronary artery diseases, cerebral artery diseases, and peripheral vascular diseases amongst others [1, 4]. Until now, most common additive risk factors for vascular disease in people with diabetes have been demonstrated as hyperglycaemia, insulin resistance, dyslipidaemia, hypertension, tobacco use, and obesity [2, 5]; however, the interaction of the

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