ABSTRACT
Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.
Subject(s)
DNA Methylation/genetics , Epigenesis, Genetic/genetics , Histone Code/genetics , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/physiopathology , RNA, Untranslated/genetics , Down-Regulation/genetics , Humans , Hypertension, Pulmonary/therapy , Molecular Targeted Therapy , Pulmonary Artery/pathology , Ubiquitination/genetics , Up-Regulation/geneticsABSTRACT
Pulmonary arterial hypertension (PAH), characterized by localized increased arterial blood pressure in the lungs, is a slow developing long-term disease that can be fatal. PAH is characterized by inflammation, vascular tone imbalance, pathological pulmonary vascular remodeling, and right-sided heart failure. Current treatments for PAH are palliative and development of new therapies is necessary. Recent and relevant studies have demonstrated that epigenetic processes may exert key influences on the pathogenesis of PAH and may be promising therapeutic targets in the prevention and/or cure of this condition. The aim of the present mini-review is to summarize the occurrence of epigenetic-based mechanisms in the context of PAH physiopathology, focusing on the roles of DNA methylation, histone post-translational modifications and non-coding RNAs. We also discuss the potential of epigenetic-based therapies for PAH.
Subject(s)
Humans , DNA Methylation/genetics , RNA, Untranslated/genetics , Epigenesis, Genetic/genetics , Histone Code/genetics , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/genetics , Pulmonary Artery/pathology , Down-Regulation/genetics , Up-Regulation/genetics , Ubiquitination/genetics , Molecular Targeted Therapy , Hypertension, Pulmonary/therapyABSTRACT
Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), including polymyxin-resistant (PR-CRE) strains, are being increasingly reported. However, there is a lack of clinical data for several life-threatening infections. Here we describe a cohort of patients with post-surgical mediastinitis due to CRE, including PR-CRE. This study was a retrospective cohort design at a single cardiology centre. Patients with mediastinitis due to CRE were identified and were investigated for clinically relevant variables. Infecting isolates were studied using molecular techniques. Patients infected with polymyxin-susceptible CRE (PS-CRE) strains were compared with those infected with PR-CRE strains. In total, 33 patients with CRE mediastinitis were studied, including 15 patients (45%) with PR-CRE. The majority (61%) were previously colonised. All infecting isolates carried blaKPC genes. Baseline characteristics of patients with PR-CRE mediastinitis were comparable with those with PS-CRE mediastinitis. Of the patients studied, 70% received at least one agent considered active in vitro and most patients received at least three concomitant antibiotics. Carbapenem plus polymyxin B was the most common antibiotic combination (73%). Over 90% of patients underwent surgical debridement. Overall, in-hospital mortality was 33% and tended to be higher in patients infected with PR-CRE (17% vs. 53%; P=0.06). In conclusion, mediastinitis due to CRE, including PR-CRE, can become a significant challenge in centres with CRE and a high cardiac surgery volume. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE.
