Final Report Summary - MIRNAVASC (Role of microRNAs in vascular diseases) We have observed that miRNA-32* and miRNA-595 are upregulated in serum from AAA patients in comparison with control healthy subjects. Furthermore, miRNA-32* and miRNA-595 administration induces apoptosis in cultured HEK cells. The involvement of these miRNAs in apoptosis could be partially explain by their regulatory effect on the antiapoptotic mediators ApoH and ATF.Abdominal aortic aneurysm (AAA)is a common aortic disease in the elderly associated with a high mortality. In contrast to other types of vascular disease which involve mainly the intima, aneurysm involves the elactic medial with a signicant loss of SMCs. Thus, although pathogenesis of the disease is not completely elucidated, apoptosis appears to represent one of the main involved processes. SMCs are the major sources of extracellular matrix proteins, and therefore, it has been postulated that depletion of SMCs may contributes to aneurysm development not only by reducing cellularity, but also by eliminating a cell population capable of directing connective tissue repair (3,36). Thus, accumulating evidence indicates that SMCs apoptosis is an early event occurring in arterial wall alteration during aneurysm development (3, 36-40), and also a underlying mechanism of aneurysm rupture (41_44). In this context, the upregulation of apoptosis-related miRNAs in serum from AAA patients observed in this study, could be related to the apoptotic process occurring into the arteria wall. In addition, some studies has revealed that blockage of apoptosis remarkably reduces both the incidence and severity of induced aneurysm in animal models (45,46). Several studies have revealed that miRNAs derived from different tissues are present in serum or plasma. Thus, the incresed expression of miRNA-595 and miRna-32* in cells underlying apoptosis could explain the origin of the circulating miRNAs in AAA patients. Analysis of exosomes-10 derived miRNAs by QPCR revealed that miR-595 and miR-32* are transfered by exosomes in serum. Recent studies support that microvesicles or apoptotic bodies-mediated transfer of microRNAs could be a mechanism of comunication between cells (47_49). Thus, miR-595 and miR-32*expression and release within apoptotic bodies by apoptotic SMCs could induce death of the neighboring cells or indeed in other vascular areas through their release into the blood stream. In vitro experiments that explore miRNAS loading into exosomes and transfer to SMCs will be needed to corroborate this hypothesis.Please see attached document for references and further details. Related documents final1-final-report.pdf
