Angiogenesis in Chronic Obstructive Pulmonary Disease

Angiogenesis is a crucial component of lung pathophysiology, not only in cancer but also in other disorders, such as chronic obstructive pulmonary disease (COPD). In COPD angiogenesis is definitely able to control and orchestrate the progression of airway remodeling. Herein, we provide several remarkable translational aspects of angiogenesis in COPD, exploring both basic and clinical research in this field. Indeed, we present a number of pro- and anti-angiogenic factors, which can be also used as potential biomarkers to monitor disease progression. 

This pre-print has subsequently been published at http://www.unisa.it/uploads/7100/06.pd

Coronary heart disease risk factors and mortality

This study challenges conventional wisdom that patients with more coronary heart disease (CHD) risk factors have worse outcomes following their first MI. We found that patients with multiple CHD risk factors presented much earlier in life with MI and had lower hospital mortality than patients with fewer or no risk factors. We confirmed that the high prevalence of risk factor exposure in patients with MI was consistent with the prior literature. In summary, we report an unexpected and possibly controversial association that, like all observational findings, should be considered hypothesis-generating and further explored in terms of health care provided to patients who reach the hospital alive with first MI

Tailoring mTOR-based therapy: molecular evidence and clinical challenges

The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism. The mTOR pathway is dysregulated in a number of human pathologies including cancer, diabetes, obesity, autoimmune disorders, neurological disease and aging. Ongoing clinical trials testing mTOR-targeted treatments number in the hundreds and underscore its therapeutic potential. To date mTOR inhibitors are clinically approved to prevent organ rejection, to inhibit restenosis after angioplasty, and to treat several advanced cancers. In this review we discuss the continuously evolving field of mTOR pharmacogenomics, as well as highlight the emerging efforts in identifying diagnostic and prognostic markers, including miRNAs, in order to assess successful therapeutic responses

Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes

G protein-coupled receptors (GPCRs) play a key role in cellular communication, allowing human cells to sense external cues or to talk each other through hormones or neurotransmitters. Research in this field has been recently awarded with the Nobel Prize in chemistry to Robert J. Lefkowitz and Brian K. Kobilka, for their pioneering work on beta adrenergic receptors (βARs), a prototype GPCR. Such receptors, and β2AR in particular, which is extensively distributed throughout the body, are involved in a number of pathophysiological processes. Moreover, a large amount of studies has demonstrated their participation in ageing process. Reciprocally, age-related changes in regulation of receptor responses have been observed in numerous tissues and include modifications of βAR responses. Impaired sympathetic nervous system function has been indeed evoked as at least a partial explanation for several modifications that occur with ageing. This article represents an updated presentation of the current knowledge in the field, summarizing in a systematic way the major findings of research on ageing in several organs and tissues (crime scenes) expressing βARs: heart, vessels, skeletal muscle, respiratory system, brain, immune system, pancreatic islets, liver, kidney and bone

Mechanistic role of β2 adrenergic receptor in glucose homeostasis

In the present article, Wang, Liu, Fu and colleagues report that β2-adrenergic receptor (β2AR) plays a key role in hyperinsulinemia-induced cardiac dysfunction.(1) Overall, the data are very interesting and compelling. However, we noticed that in this paper β2AR-/- mice do not exhibit glucose intolerance; in fact, they seem to have a response to intraperitoneal glucose that is even better than wild-type mice (though a statistical analysis comparing these two groups is not provided). Although surprisingly not reported by the Authors, mounting evidence indicates that the deletion of β2AR has detrimental effects on glucose metabolism.(2-4) Indeed, we have demonstrated that β2AR-/- mice display impaired insulin release and significant glucose intolerance.(2) Muzzin and colleagues found that the ablation of βARs mechanistically underlies impaired glucose homeostasis.(3) Other groups have confirmed these results, also showing that β2AR-/- mice develop diabetic-related microvascular complications (i.e. retinopathy)(4). Nonetheless, the Authors fail to at least discuss previous relevant literature describing the alterations in glucose metabolism observed in β2AR-/- mice and do not accurately circumstantiate their findings. Furthermore, the Authors do not provide any measurement (not in vivo nor in isolated islets) of insulin levels following glucose challenge, showing just baseline serum levels. We believe that for the sake of scientific appropriateness the Readers of Circulation will appreciate a clarification, in particular regarding the fact that pertinent literature in the field has been overlooked

CRT prevents new-onset AF

SUMMARY Aim: The aim of this study was to determine whether or not cardiac resynchronization therapy (CRT) has a favourable effect on the incidence of new-onset atrial fibrillation (AF) in a homogeneous population of patients with non-ischaemic idiopathic-dilated cardiomyopathy and severe heart failure. Methods: We designed a single-centre prospective study and enrolled 58 patients AF nao¨ve when received CRT. After 1 year of follow-up our population was subdivided into responders (72.4%) and non-responders (27.6%), so as to compare the incidence of AF after 1, 2 and 3 years of follow-up in these two groups. Results: Already after 1 year, there was a significant (p < 0.05) difference in new-onset AF in non-responder patients with respect to responders (18.2% vs. 3.3%). These data were confirmed at 2 years (33.3% vs. 12.2%) and 3 years (50.0% vs. 15.0%) follow-up. In particular, 3 years after device implantation non-responders had an increased risk to develop new-onset AF (OR = 5.67). Conclusions: This is the first study analysing long-term effects of CRT in a homogeneous population of patients with nonischaemic dilated cardiomyopathy, indicating the favourable role of this non-pharmacological therapy on the prevention of AF. What's known Albeit several studies examined the association between cardiac resynchronization therapy and atrial fibrillation in heart failure, results are still unclear and quite conflicting. What's new In this study we show that in patients with non-ischemic dilated cardiomyopathy a positive response to cardiac resynchronization therapy has a favorable role on the prevention of new-onset atrial fibrillation.

Role of cardiac resynchronization therapy in the development of new-onset atrial fibrillation: A single-center prospective study.

Albeit several studies examined the association between cardiac resynchronization therapy (CRT) and atrial fibrillation (AF) in heart failure (HF), results are still unclear and quite conflicting. We thereby designed a single-center prospective study to determine whether CRT has a favorable effect on the incidence of new-onset AF in a homogeneous population of patients with non-ischemic idiopathic dilated cardiomyopathy and severe heart failure HF. We enrolled 58 patients, AF na&#xef;ve when received CRT. After 1 year of follow-up our population was subdivided into responders (72.4%) and non (27.6%), so to compare the incidence of AF after 1, 2 and 3 years of follow-up in these two groups. Already after 1 year, there is a significant (p&#x3c;0.05) difference in new-onset AF in non-responder patients respect to responders (18.2% vs 3.3%). These data are confirmed at 2 year (33.3% vs 12.2%) and 3 year (50.0% vs 15.0%) follow-up. In particular, at 3 year follow-up, non-responders have an increased risk to develop new-onset AF (OR=5.67, 95% confidence interval = 1.36-23.59, p=0.019). The present work suggests a possible favorable role of this non-pharmacological therapy, on the prevention of AF