Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability

Endothelial to mesenchymal transition (EndMT) plays a major role during development, and also contributes to several adult cardiovascular diseases. Importantly, mesenchymal cells including fibroblasts are prominent in atherosclerosis, with key functions including regulation of: inflammation, matrix and collagen production, and plaque structural integrity. However, little is known about the origins of atherosclerosis-associated fibroblasts. Here we show using endothelial-specific lineage-tracking that EndMT-derived fibroblast-like cells are common in atherosclerotic lesions, with EndMT-derived cells expressing a range of fibroblast-specific markers. In vitro modelling confirms that EndMT is driven by TGF-β signalling, oxidative stress and hypoxia; all hallmarks of atherosclerosis. ‘Transitioning' cells are readily detected in human plaques co-expressing endothelial and fibroblast/mesenchymal proteins, indicative of EndMT. The extent of EndMT correlates with an unstable plaque phenotype, which appears driven by altered collagen-MMP production in EndMT-derived cells. We conclude that EndMT contributes to atherosclerotic patho-biology and is associated with complex plaques that may be related to clinical events

Impact of mitral regurgitation on the outcome of patients treated with CRT-D: data from the InSync ICD Italian Registry.

Background: We assessed the influence of clinically significant mitral regurgitation (MR) on clinical-echocardiographic response and outcome in heart failure (HF) patients treated with a biventricular defibrillator (cardiac resynchronization therapy defibrillator [CRT-D]). Methods and Results: A total of 659 HF patients underwent successful implantation of CRT-D and were enrolled in a multicenter prospective registry (median follow-up of 15 months). Following baseline echocardiographic evaluation, patients were stratified into two groups according to the severity of MR: 232 patients with more than mild MR (Group MR+: grade 2, 3, and 4 MR) versus 427 patients with mild (grade 1) or no functional MR (Group MR−). On 6- and 12-month echocardiographic evaluation, MR was seen to have improved in the vast majority of MR+ patients, while it remained unchanged in most MR− patients. On 12-month follow-up evaluation, a comparable response to CRT was observed in the two groups, in terms of the extent of left ventricular reverse remodeling and combined clinical and echocardiographic response. During long-term follow-up, event-free survival did not differ between MR+ and MR− patients, even when subpopulations of patients with ischemic heart disease and with dilated cardiomyopathy were analyzed separately. On multivariate analysis, the only independent predictor of death from any cause was the lack of β-blocker use. Conclusions: This observational analysis supports the use of CRT-D in HF patients with clinically significant MR; MR had no major influence on patient outcom

The Role of MicroRNAs in Diabetic Complications—Special Emphasis on Wound Healing

Overweight and obesity are major problems in today’s society, driving the prevalence of diabetes and its related complications. It is important to understand the molecular mechanisms underlying the chronic complications in diabetes in order to develop better therapeutic approaches for these conditions. Some of the most important complications include macrovascular abnormalities, e.g., heart disease and atherosclerosis, and microvascular abnormalities, e.g., retinopathy, nephropathy and neuropathy, in particular diabetic foot ulceration. The highly conserved endogenous small non-coding RNA molecules, the micro RNAs (miRNAs) have in recent years been found to be involved in a number of biological processes, including the pathogenesis of disease. Their main function is to regulate post-transcriptional gene expression by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation, suppression of translation or even gene activation. These molecules are promising therapeutic targets and demonstrate great potential as diagnostic biomarkers for disease. This review aims to describe the most recent findings regarding the important roles of miRNAs in diabetes and its complications, with special attention given to the different phases of diabetic wound healing

L’attività dei Centri Antifumo italiani tra problematiche e aree da potenziare: i risultati di un’indagine svolta attraverso un questionario on-line

Introduzione. In Italia sono 295 i Servizi per la cessazione dal fumo di tabacco (Centri Antifumo - CA) afferenti al Servizio Sanitario Nazionale (SSN) censiti nel 2011 dall’Osservatorio Fumo, Alcol e Droga (OssFAD) dell’Istituto Superiore di Sanità. La presente indagine, condotta dall’OssFAD in collaborazione con i CA, è stata volta a rilevare alcune delle problematiche con le quali il personale dei CA si confronta per portare avanti la propria attività e le iniziative ritenute utili per migliorarla. Materiali e metodi. L’indagine è stata condotta dal 7 al 21 maggio 2012, mediante un questionario compilabile on-line composto da 5 brevi sezioni di domande con un totale di 38 items da completare. Il link al questionario on-line è stato inviato per e-mail a 322 indirizzi dei CA censiti nel 2011 dall’OssFAD. I dati raccolti sono stati elaborati statisticamente con il programma SPSS 20. Risultati. All’indagine hanno risposto 146 operatori dei CA (45,3%). Sebbene ci siano aspetti ormai consolidati dell’attività dei CA, sono ancora molte le criticità che gli operatori riscontrano nella loro attività. Le principali problematiche che influiscono in modo fondamentale/rilevante per la buona attività del centro sono le “Scarse o nulle risorse economiche” per il 60,7% del personale, “la mancanza di personale dedicato” per il 52,4% del personale; il “riconoscimento/mandato istituzionale del CA” per il 40,9% del personale. Tra le azioni ritenute più efficaci per facilitare l’accesso ai CA sono risultate la sensibilizzazione del personale sanitario (91%), in particolare dei medici di famiglia e l’inserimento delle prestazioni antitabagiche nei LEA (76,8%). Conclusioni. È auspicabile che l’attività dei CA riceva una maggiore attenzione, attraverso la dotazione di strutture, personale e finanziamenti adeguati a svolgere un importante ruolo nella tutela e promozione della salute