Background: Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. Methods: We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77–81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Results: Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574–1971 pg/mL vs. 775, 95% CI 600–950 pg/mL, respectively, p < 0.0001). Subjects in the upper GDF15 tertile were older (p = 0.004), with a more advanced NYHA functional class (p = 0.04) and a higher prevalence of impaired renal function (p = 0.004). Such patients also showed a higher frailty score (p = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain (p = 0.01) and a higher left ventricular mass (p = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9–1.1; p = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. Conclusions: GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients’ frailty, independent of indices of left ventricular dysfunction.

Cherries are known for their nutraceutical properties, in particular for their antioxidant ability due to their polyphenol content, which causes a reduction of cardiovascular disease (CVD) risk factors. However, once ingested these molecules are degraded in the Gastrointestinal (GI) tract before reaching the blood, which is the action site. The object of the present work is to evaluate the ability of cherry extract (CE), encapsulated in nanoparticles (NPs) based on different chitosan (Ch) derivatives, to promote a protective effect of human umbilical vein endothelial cells (HUVECs) involved in vascular dysfunction against oxidative stress. CE-loaded NPs based on quaternary ammonium chitosan (NP1) and an S-protected thiolated derivative thereof (NP2) were prepared. The mean particle size (NP1 344.9 ± 17.8, NP2 339.9 ± 68.2 nm), the polydispersity index, the encapsulation efficiency (NP1 78.4 ± 4.5, NP2 79.8 ± 0.6%), and the zeta potential (NP1 14.8 ± 0.3, NP2 15.8 ± 0.5 mV) did not appear to be significantly different. Both NP types improved the CE apparent permeation parameters with respect to the control. Conversely, CE-loaded NP2 protected HUVECs from oxidative stress and reduced reactive oxygen species (ROS) production more than CE-loaded NP1 and free CE. In addition to promoting HUVEC resistance, NP2 could be a useful tool to overcome the problem of cherry seasonality.

Objectives Aminaphtone, a naphtohydrochinone used in the treatment of capillary disorders, may affect oedema in chronic venous insufficiency. Aim of study is to investigate the effect of aminaphtone on vascular endothelial permeability in vitro and its effects on three-dimensional capillary-like structures formed by human umbilical vein endothelial cells. Method Human umbilical vein endothelial cells were treated with 50 ng/ml VEGF for 2 h and aminaphtone for 6 h. Permeability assay, VE-cadherin expression and Matrigel assay were performed. Results VEGF-induced permeability was significantly decreased by aminaphtone in a range concentration of 1–20 µg/ml. Aminaphtone restored VE-cadherin expression. Finally, 6 h pre-treatment with aminaphtone significantly preserved capillary-like structures formed by human umbilical vein endothelial cells on Matrigel up to 48 h compared to untreated cells. Conclusions Aminaphtone significantly protects endothelium permeability and stabilises endothelial cells organised in capillary-like structures, modulating VE-cadherin expression. These data might explain the clinical benefit of aminaphtone on chronic venous insufficiency.

Endothelial progenitor cells (EPCs) contribute to ischemic tissue repair by paracrine secretion up-regulated by hypoxia. In this study we use novel nanoparticles (NPs) as carriers for a controlled release of EPC secretome (CM) to improve their angiogenic properties. The in vivo effect in ischemic hindlimb rat model was evaluated, comparing hypoxic EPC-CM-NPs with hypoxic EPC-CM alone. A proteomic characterization of hypoxic CM and the in vitro effect on endothelial cells (HUVECs) were also performed. Up to 647 protein, 17 of which with angiogenic properties, were upregulated by hypoxia. Moreover, hypoxic EPC-CM significantly promoted capillary-like structures on Matrigel. A significant increase of blood perfusion in ischemic limbs at 2 weeks with EPCCM-loaded NPs as compared to both EPC-CM and control and a significant increase of capillary formation were observed. The use of EPC-CM-NPs significantly improved neoangiogenesis in vivo, underlining the advantages of controlled release in regenerative medicine.

Aortic valve stenosis (AVS) is associated with significant myocardial fibrosis (MF). Global longitudinal strain (GLS) is a sensible indicator of systolic dysfunction. ST2 is a member of the interleukin (IL)-1 receptor family and a modulator of hypertrophic and fibrotic responses. We aimed at assessing: (a) the association between adverse LV remodeling, LV functional parameters (including GLS) and sST2 level. (b) The association between MF (detected by endo-myocardial biopsy) and sST2 in patients with AVS undergoing surgical valve replacement. Twenty-two patients with severe AVS and preserved EF underwent aortic valve replacement. They performed laboratory analysis, including serum ST2 (sST2), echocardiography and inter-ventricular septum biopsy to assess MF (%). We included ten controls for comparison. Compared to controls, patients showed higher sST2 levels (p < 0.0001). sST2 showed correlation with Age (r = 0.58; p = 0.0004), E/e′ average (r = 0.58; p = 0.0007), GLS (r = 0.61; p = 0.0002), LAVi (r = 0.51; p = 0.003), LVMi (r = 0.43; p = 0.01), sPAP (r = 0.36; p = 0.04) and SVi (r = −0.47; p < 0.005). No correlation was found between MF and sST2. At ROC analysis, a sST2 ≥ 284 ng/mL had the best accuracy to discriminate controls from patients with impaired GLS, i.e. GLS ≤ 17% (AUC 0.80; p = 0.003; sensitivity 95%; specificity 83%) and increased E/e′ average (AUC 0.87; p = 0.0001; sensitivity 96%; specificity 74%). At multivariate regression analysis GLS resulted the only independent predictor of sST2 levels (R2 = 0.35; p =  0.0004). Patients with severe AVS present elevated sST2 levels. LV GLS resulted the only independent predictor of sST2 levels.

Different strategies have been developed to make the wound-healing process faster and less painful. Recently, numerous studies demonstrated the ability of chitosan to accelerate wound healing. Aim of the present study has been to evaluate the effect of different chitosan derivatives to improve wound healing process. Quaternary ammonium-chitosan conjugates with low or high molecular weight (MW) and their thiolated derivatives effect were studied on human skin fibroblasts in terms of viability and migration (scratch wound assay). Results were compared both with basal medium (untreated cells) and with a positive control (chitosan chlorhydrate). After 24h both high and low MW chitosan derivatives were non-toxic up to 10 μg/ml. The concentration of 10 μg/ml was used for wound healing experiments. High-MW quaternary ammonium-chitosan conjugates bearing thiol groups on their chains were more effective in promoting cell migration than the non-thiolated conjugates and the chitosan chlorhydrate. Moreover, they significantly improve wound healing process compared to untreated cells. According to the present in vitro preliminary results, high MW thiolated quaternary ammonium-chitosan conjugates can be considered good candidates for the management of wounds.

Endothelialprogenitorcells(EPCs)aremobilizedfrombonemarrowinto peripheral blood, contributing to the revascularization of ischemicareas, to endothelial repair and to the physiological maintenance ofvascularization. EPC mobilization and homing have been primarilylinked to ischemia and inflammation presence [1]. EPCs are directlycorrelated with endothelial function and inversely correlated withcardiovascular risk factors and atherosclerosis progression [2].EPClevelshavealsobeencorrelatedtoprognosisevaluationincardiovascu-lar disease [3].Regarding EPC correlation with coronary artery disease (CAD)presence and severity, an inverse relationship with CAD severity, inde-pendent of traditional risk factors, was demonstrated by EPC colonycounting [4],whileahighnumberofEPCsassociatedwithCADandcorre-latedwithstenosisseveritywereshownby flowcytometry [5].Recentlyanew protocol, adapted from the standardized ISHAGE protocol for hema-topoieticstemcells,hasbeendevelopedforEPClevelevaluationtoenablecomparison of clinical and laboratory data [6].While thepresence of circulatingEPCshasbeenwidely evaluated indifferent diseases, few studies tried to evaluate the presence of EPCs inhuman vital myocardium.TheaimofourstudywastoinvestigateEPClevelsbothinperipheralbloodand inmyocardium in thesame patients atthesame time, evalu-atingthecorrelationwith CADpresence. In bothsampleswequantifiedCD34

No scientific evidence concerning the presence and role of endothelial progenitor cells (EPCs) in human vital myocardium exists. This study aimed to investigate the correlation between peripheral and myocardial EPC number and coronary artery disease (CAD) severity. 12 consecutive CAD patients, 5

Background Foam sclerotherapy has been proven to be a safe and effective treatment for superficial venous insufficiency, but transient visual and neurologic disturbances continue to be reported. These side effects have been theorized to be related to the presence of air or gases in the sclerosing foam that results in “bubble” migration into the cerebral circulation. We present a differing hypothesis that significant amounts of endothelin are released from the treated veins, amounts capable of causing these complications. Material and Methods We tested the release of endothelin 1 (ET-1) in 12 rats after sclerotherapy with sodium tetradecyl sulfate (STS) in liquid and foam preparations. In 11 human subjects, we measured ET-1 in systemic circulation and in a draining vein after foam sclerotherapy with polidocanol. Results Rats treated with STS showed a significant increase in ET-1 levels 1 and 5 minutes after foam sclerotherapy. Patients treated with foam sclerotherapy showed a marked increase in ET-1 levels that correlated significantly with local ET-1 levels. Conclusions Evidence of ET-1 release represents a plausible relationship explaining neurologic and visual disturbances reported after sclerotherapy.