Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway.

AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated. METHODS: The effect of incretin therapy in the regulation of adiponectin/APPL1 signaling was evaluated both on carotid plaques of asymptomatic diabetic (n=71) and non-diabetic patients (n=52), and through in vitro experiments on endothelial cell (EC). RESULTS: Atherosclerotic plaques of T2DM patients showed lower adiponectin and APPL1 levels compared with non-diabetic patients, along with higher oxidative stress, tumor necrosis factor-α (TNF-α), vimentin, and matrix metalloproteinase-9 (MMP-9) levels. Among T2DM subjects, current incretin-users presented higher APPL1 and adiponectin content compared with never incretin-users. Similarly, in vitro observations on endothelial cells co-treated with high-glucose (25mM) and GLP-1 (100nM) showed a greater APPL1 protein expression compared with high-glucose treatment alone. CONCLUSIONS: Our findings suggest a potential role of adiponectin/APPL1 signaling in mediating the effect of incretin in the prevention of atherosclerosis progression or plaque vulnerability in T2DM.

Acute aortic syndromes at high surgical risk: the endovascular approach.

AIMS: Acute aortic syndromes (AAS) still represent life-threatening conditions. The aim of this study was to describe our experience in the management of patients (pts) with AAS and to evaluate the safety and feasibility of endovascular treatment (EVT) in high surgical risk patients. METHODS AND RESULTS: One hundred and four patients underwent EVT. We selected 56 pts with AAS: 17 complicated type B aortic dissections, five traumatic aortic ruptures at the isthmus, 11 thoracic aneurysms and 23 pts with large AAA with impending rupture. All these pts were at high surgical risk because of their comorbidities and/or their emergency situation. They were clinically followed during hospitalisation and they underwent a 2 mm-interval CT-scan two weeks, six and 12 months after discharge and every year after. Death, paraplegia, open surgical conversion did not occur. Two pts underwent a successful secondary EVT for type I endoleak. One patient with thoracic aortic aneurysm died of septic shock from pneumonia 78 days after discharge and two pts with AAA suffering from a severe three-vessel coronary disease experienced sudden death at one year follow-up. CONCLUSIONS: EVT seems to be a safe and effective therapeutic option with good short- and midterm results in patients with AAS at high surgical risk. Thus, it can be considered as a less-invasive alternative in patients considered otherwise unsuitable for conventional surgery, even though a careful, continued follow-up is still necessary to confirm the long-term safety and effectiveness of EVT in AAS.