Project description:RNA epigenetics is perhaps the most recent field of interest for translational epigeneticists. RNA modifications create such an extensive network of epigenetically driven combinations whose role in physiology and pathophysiology is still far from being elucidated. Not surprisingly, some of the players determining changes in RNA structure are in common with those involved in DNA and chromatin structure regulation, while other molecules seem very specific to RNA. It is envisaged, then, that new small molecules, acting selectively on RNA epigenetic changes, will be reported soon, opening new therapeutic interventions based on the correction of the RNA epigenetic landscape. In this review, we shall summarize some aspects of RNA epigenetics limited to those in which the potential clinical translatability to cardiovascular disease is emerging.
Project description:Cardiovascular diseases are the number one cause of death worldwide and greatly impact quality of life and medical costs. Enormous effort has been made in research to obtain new tools for efficient and quick diagnosis and predicting the prognosis of these diseases. Discoveries of epigenetic mechanisms have related several pathologies, including cardiovascular diseases, to epigenetic dysregulation. This has implications on disease progression and is the basis for new preventive strategies. Advances in methodology and big data analysis have identified novel mechanisms and targets involved in numerous diseases, allowing more individualized epigenetic maps for personalized diagnosis and treatment. This paves the way for what is called pharmacoepigenetics, which predicts the drug response and develops a tailored therapy based on differences in the epigenetic basis of each patient. Similarly, epigenetic biomarkers have emerged as a promising instrument for the consistent diagnosis and prognosis of cardiovascular diseases. Their good accessibility and feasible methods of detection make them suitable for use in clinical practice. However, multicenter studies with a large sample population are required to determine with certainty which epigenetic biomarkers are reliable for clinical routine. Therefore, this review focuses on current discoveries regarding epigenetic biomarkers and its controversy aiming to improve the diagnosis, prognosis, and therapy in cardiovascular patients.
Project description:In recent years, technological advances in sequencing have accelerated our understanding of epigenetics in ocular development and ophthalmic diseases. We now know that epigenetic modifications are necessary for normal ocular development and biological processes such as corneal wound healing and ocular surface repair, while aberrant epigenetic regulation underlies the pathogenesis of a wide range of ocular diseases, including cataracts and various diseases of the ocular surface. As the epigenetics of the eye is a constantly changing field of medicine, this comprehensive review focuses on innovations and scientific discoveries related to epigenetic control of anterior segment diseases that were published in the English literature in the past five years. These recent studies attempt to elucidate therapeutic targets for the anterior segment pathological processes. Already, recent studies have shown therapeutic potential in targeting epigenetic mechanisms of ocular diseases, and new epigenetic therapies are on the verge of being introduced to clinical practice. New drug targets can potentially emerge as we make further discoveries within this field.
Project description:Sympathetic overactivation plays an important role in promoting a variety of pathophysiological processes in cardiovascular diseases (CVDs), including ventricular remodeling, vascular endothelial injury and atherosclerotic plaque progression. Device-based sympathetic nerve (SN) regulation offers a new therapeutic option for some CVDs. Renal denervation (RDN) is the most well-documented method of device-based SN regulation in clinical studies, and several large-scale randomized controlled trials have confirmed its value in patients with resistant hypertension, and some studies have also found RDN to be effective in the control of heart failure and arrhythmias. Pulmonary artery denervation (PADN) has been clinically shown to be effective in controlling pulmonary hypertension. Hepatic artery denervation (HADN) and splenic artery denervation (SADN) are relatively novel approaches that hold promise for a role in cardiovascular metabolic and inflammatory-immune related diseases, and their first-in-man studies are ongoing. In addition, baroreflex activation, spinal cord stimulation and other device-based therapies also show favorable outcomes. This review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for some CVDs.
Project description:Preeclampsia (PE) is the major pregnancy-induced hypertensive disorder responsible for maternal and fetal morbidity and mortality that can be associated with intrauterine growth restriction (IUGR). PE and IUGR are thought to be due to a placental defect, occurring early during pregnancy. Several placental microRNAs (miRNAs) have been shown to be deregulated in the context of placental diseases and could thus play a role in the pathophysiology of PE. Here, we show that pri-miR-34a is overexpressed in preeclamptic placentas and that its placental expression is much higher during the first trimester of pregnancy than at term, suggesting a possible developmental role. We explored pri-miR-34a regulation and showed that P53, a known activator of miR-34a, is reduced in all pathological placentas and that hypoxia can induce pri-miR-34a expression in JEG-3 cells. We also studied the methylation status of the miR-34a promoter and revealed hypomethylation in all preeclamptic placentas (associated or not with IUGR), whereas hypoxia induced a hypermethylation in JEG-3 cells at 72 h. Despite the overexpression of pri-miR-34a in preeclampsia, there was a striking decrease of the mature miR-34a in this condition, suggesting preeclampsia-driven alteration of pri-miR-34a maturation. SERPINA3, a protease inhibitor involved in placental diseases, is elevated in IUGR and PE. We show here that miR-34a overexpression in JEG-3 downregulates SERPINA3. The low level of mature miR-34a could thus be an important mechanism contributing to SERPINA3 upregulation in placental diseases. Overall, our results support a role for miR-34a in the pathophysiology of preeclampsia, through deregulation of the pri-miRNA expression and its altered maturation.
Project description:Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined "ageing epigenome". The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies.