Cardiovascular disease (CVD) is the most important cause of death and illness in the western world. Atherosclerosis constitutes the single most important contributor to CVD. miRNAs are small ribonucleic acids (RNAs) that negatively regulate gene expression on the post-transcriptional level by inhibiting mRNA translation or promoting mRNA degradation. Several studies demonstrated that miRNAs dysregulation have a key role in the disease process and, focusing on atherosclerotic disease, in every step of plaque formation and destabilization. These data suggest a possible therapeutic application of miRNA modulation, in particular dysregulated miRNAs can be modulated in disease process antagonizing miRNAs up-regulated and increasing miRNAs down-regulated. In this review we summarize the miRNA therapeutic techniques (antimiR, mimics, sponges, masking, and erasers) underlining their therapeutic advantages and evaluating their risks and challenges. In particular, the use of miRNA modulators as a therapeutic approach opens a novel and fascinating area of intervention in the therapy of ischemic heart disease.
Diabetes mellitus (DM) is a pandemics that affects more than 170 million people worldwide, associated with increased mortality and morbidity due to coronary artery disease (CAD). In type 1 (T1) DM, the main pathogenic mechanism seems to be the destruction of pancreatic β-cells mediated by autoreactive T-cells resulting in chronic insulitis, while in type 2 (T2) DM primary insulin resistance, rather than defective insulin production due to β-cell destruction, seems to be the triggering alteration. In our study, we investigated the role of systemic inflammation and T-cell subsets in T1- and T2DM and the possible mechanisms underlying the increased cardiovascular risk associated with these diseases.
Activated PMNs were shown to produce and release reactive oxygen species, inflammatory leukotrienes and proteolytic lysosomal enzymes, directly inducing vascular damage. Activated PMNs also secrete myeloperoxidase, involved in lipoprotein oxidation. PMNs have a finite lifespan and typically die through apoptosis, which thus represents a counter-regulatory mechanism limiting the toxic potential of these short-lived, terminally differentiated cells. Dysregulation of this process probably contributes to the pathogenesis and progression of several inflammatory diseases. Moreover, high circulating levels of PMN-platelet aggregates have been reported in patients with clinical atherosclerosis, and recent studies suggest that these aggregates may play a role in vascular response to injury. It has been suggested that this heterotypic interaction between platelets and leukocytes might represent a link between hemostasis/thrombosis and the inflammatory response.
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