San Donato di Ninea, Italy
San Donato di Ninea, Italy

Time filter

Source Type

PubMed | 1 Molecular Cardiology Laboratory
Type: Journal Article | Journal: Antioxidants & redox signaling | Year: 2014

MicroRNAs (miRNAs) are deregulated and play a causal role in numerous cardiovascular diseases, including myocardial infarction, coronary artery disease, hypertension, heart failure, stroke, peripheral artery disease, kidney ischemia-reperfusion.One crucial component of ischemic cardiovascular diseases is represented by hypoxia. Indeed, hypoxia is a powerful stimulus regulating the expression of a specific subset of miRNAs, named hypoxia-induced miRNAs (hypoxamiR). These miRNAs are fundamental regulators of the cell responses to decreased oxygen tension. Certain hypoxamiRs seem to have a particularly pervasive role, such as miR-210 that is virtually induced in all ischemic diseases tested so far. However, its specific function may change according to the physiopathological context.The discovery of HypoxamiR dates back 6 years. Thus, despite a rapid growth in knowledge and attention, a deeper insight of the molecular mechanisms underpinning hypoxamiR regulation and function is needed.An extended understanding of the function of hypoxamiR in gene regulatory networks associated with cardiovascular diseases will allow the identification of novel molecular mechanisms of disease and indicate the development of innovative therapeutic approaches.


PubMed | 1 Molecular Cardiology Laboratory
Type: Journal Article | Journal: Antioxidants & redox signaling | Year: 2014

Peripheral artery disease is caused by the restriction or occlusion of arteries supplying the leg. Better understanding of the molecular mechanisms underpinning tissue response to ischemia is urgently needed to improve therapeutic options. The aim of this study is to investigate hypoxia-induced miR-210 regulation and its role in a mouse model of hindlimb ischemia.miR-210 expression was induced by femoral artery dissection. To study the role of miR-210, its function was inhibited by the systemic administration of a miR-210 complementary locked nucleic acid (LNA)-oligonucleotide (anti-miR-210). In the ischemic skeletal muscle, anti-miR-210 caused a marked decrease of miR-210 compared with LNA-scramble control, while miR-210 target expression increased accordingly. Histological evaluation of acute tissue damage showed that miR-210 inhibition increased both apoptosis at 1 day and necrosis at 3 days. Capillary density decrease caused by ischemia was significantly more pronounced in anti-miR-210-treated mice; residual limb perfusion decreased accordingly. To investigate the molecular mechanisms underpinning the increased damage triggered by miR-210 blockade, we tested the impact of anti-miR-210 treatment on the transcriptome. Gene expression analysis highlighted the deregulation of mitochondrial function and redox balance. Accordingly, oxidative damage was more severe in the ischemic limb of anti-miR-210-treated mice and miR-210 inhibition increased oxidative metabolism. Further, oxidative-stress resistant p66(Shc)-null mice displayed decreased tissue damage following ischemia.This study identifies miR-210 as a crucial element in the adaptive mechanisms to acute peripheral ischemia.The physiopathological significance of miR-210 is context dependent. In the ischemic skeletal muscle it seems to be cytoprotective, regulating oxidative metabolism and oxidative stress.

Loading 1 Molecular Cardiology Laboratory collaborators
Loading 1 Molecular Cardiology Laboratory collaborators