A segmental approach from molecular profiling to medical imaging to study bicuspid aortic valve aortopathy

Bicuspid aortic valve (BAV) patients develop ascending aortic (AAo) dilation. The pathogenesis of BAV aortopathy (genetic vs. haemodynamic) remains unclear. This study aims to identify regional changes around the AAo wall in BAV patients with aortopathy, integrating molecular data and clinical imaging. BAV patients with aortopathy (n = 15) were prospectively recruited to surgically collect aortic tissue and measure molecular markers across the AAo circumference. Dilated (anterior/right) vs. non-dilated (posterior/left) circumferential segments were profiled for whole-genomic microRNAs (next-generation RNA sequencing, miRCURY LNA PCR), protein content (tandem mass spectrometry), and elastin fragmentation and degeneration (histomorphometric analysis). Integrated bioinformatic analyses of RNA sequencing and proteomic datasets identified five microRNAs (miR-128-3p, miR-210-3p, miR-150-5p, miR-199b-5p, and miR-21-5p) differentially expressed across the AAo circumference. Among them, three miRNAs (miR-128-3p, miR-150-5p, and miR-199b-5p) were predicted to have an effect on eight common target genes, whose expression was dysregulated, according to proteomic analyses, and involved in the vascular-endothelial growth-factor signalling, Hippo signalling, and arachidonic acid pathways. Decreased elastic fibre levels and elastic layer thickness were observed in the dilated segments. Additionally, in a subset of patients n = 6/15, a four-dimensional cardiac magnetic resonance (CMR) scan was performed. Interestingly, an increase in wall shear stress (WSS) was observed at the anterior/right wall segments, concomitantly with the differentially expressed miRNAs and decreased elastic fibres. This study identified new miRNAs involved in the BAV aortic wall and revealed the concomitant expressional dysregulation of miRNAs, proteins, and elastic fibres on the anterior/right wall in dilated BAV patients, corresponding to regions of elevated WSS

Off-pump coronary artery bypass grafting in high-risk patients: A review

The role of off-pump coronary artery bypass (OPCAB) grafting in high risk patients remains controversial. While there have been studies showing the potential benefits of it, there is still a lot to be learned from the application of this technique in this sub-group of patients. The results of the different trials and papers that we reviewed seem to indicate a benefit in the OPCAB group. Despite of the fact that trials were significantly different in methodology, especially when choosing the risk score stratification tool or the cut-off to define high risk the literature seems to suggest a benefit from the use of OPCAB surgery. Here, we present a review which focussed on early and late outcome in high risk patients undergoing on- and off-pump coronary revascularization

Interventions to Address Cardiovascular Risk in Obese Patients: Many Hands Make Light Work

Obesity is a growing public health epidemic worldwide and is implicated in slowing improved life expectancy and increasing cardiovascular (CV) risk; indeed, several obesity-related mechanisms drive structural, functional, humoral, and hemodynamic heart alterations. On the other hand, obesity may indirectly cause CV disease, mediated through different obesity-associated comorbidities. Diet and physical activity are key points in preventing CV disease and reducing CV risk; however, these strategies alone are not always sufficient, so other approaches, such as pharmacological treatments and bariatric surgery, must support them. Moreover, these strategies are associated with improved CV risk factors and effectively reduce the incidence of death and CV events such as myocardial infarction and stroke; consequently, an individualized care plan with a multidisciplinary approach is recommended. More precisely, this review explores several interventions (diet, physical activity, pharmacological and surgical treatments) to address CV risk in obese patients and emphasizes the importance of adherence to treatments

Ezrin is a novel protein partner of aquaporin-5 in human salivary glands and shows altered expression and cellular localization in sjögren’s syndrome

Sjögren’s syndrome (SS) is an exocrinopathy characterized by the hypofunction of salivary glands (SGs). Aquaporin-5 (AQP5); a water channel involved in saliva formation; is aberrantly dis-tributed in SS SG acini and contributes to glandular dysfunction. We aimed to investigate the role of ezrin in AQP5 mislocalization in SS SGs. The AQP5–ezrin interaction was assessed by immuno-precipitation and proteome analysis and by proximity ligation assay in immortalized human SG cells. We demonstrated, for the first time, an interaction between ezrin and AQP5. A model of the complex was derived by computer modeling and in silico docking; suggesting that AQP5 interacts with the ezrin FERM-domain via its C-terminus. The interaction was also investigated in human minor salivary gland (hMSG) acini from SS patients (SICCA-SS); showing that AQP5–ezrin complexes were absent or mislocalized to the basolateral side of SG acini rather than the apical region compared to controls (SICCA-NS). Furthermore, in SICCA-SS hMSG acinar cells, ezrin immunore-activity was decreased at the acinar apical region and higher at basal or lateral regions, accounting for altered AQP5–ezrin co-localization. Our data reveal that AQP5–ezrin interactions in human SGs could be involved in the regulation of AQP5 trafficking and may contribute to AQP5-altered localization in SS patients

Brain and lower body protection during aortic arch surgery

BackgroundDeep hypothermic circulatory arrest (DHCA) at <= 20 degrees C for aortic arch surgery has been widely used for decades, with or without cerebral perfusion (CP), antegrade (antegrade cerebral perfusion [ACP]), or retrograde. In recent years nadir temperature progressively increased to 26 degrees C-28 degrees C (moderately hypothermic circulatory arrest [MHCA]), adding ACP. Aim of this multicentric study is to evaluate early results of aortic arch surgery and if DHCA with 10 min of cold reperfusion at the same nadir temperature of the CA before rewarming (delayed rewarming [DR]) can provide a neuroprotection and a lower body protection similar to that provided by MHCA + ACP. MethodsA total of 210 patients were included in the study. DHCA + DR was used in 59 patients and MHCA + ACP in 151. Primary endpoints were death, neurologic event (NE), temporary (TNE), or permanent (permanent neurologic deficit [PND]), and need of renal replacement therapy (RRT). ResultsOperative mortality occurred in 14 patients (6.7%), NEs in 17 (8.1%), and PNDs in 10 (4.8%). A total of 23 patients (10.9%) needed RRT. Death + PND occurred in 21 patients (10%) and composite endpoint in 35 (19.2%). Intergroup weighed logistic regression analysis showed similar prevalence of deaths, NDs, and death + PND, but need of RRT (odds ratio [OR]: 7.39, confidence interval [CI]: 1.37-79.1) and composite endpoint (OR: 8.97, CI: 1.95-35.3) were significantly lower in DHCA + DR group compared with MHCA + ACP group. ConclusionsThe results of our study demonstrate that DHCA + DR has the same prevalence of operative mortality, NE and association of death+PND than MHCA + ACP. However, the data suggests that DHCA + DR when compared with MHCA + ACP provides better renal protection and reduced prevalence of composite endpoint

Unraveling human aqp5-pip molecular interaction and effect on aqp5 salivary glands localization in ss patients

Saliva secretion requires effective translocation of aquaporin 5 (AQP5) water channel to the salivary glands (SGs) acinar apical membrane. Patients with Sjögren’s syndrome (SS) display abnormal AQP5 localization within acinar cells from SGs that correlate with sicca manifestation and glands hypofunction. Several proteins such as Prolactin-inducible protein (PIP) may regulate AQP5 trafficking as observed in lacrimal glands from mice. However, the role of the AQP5-PIP complex remains poorly understood. In the present study, we show that PIP interacts with AQP5 in vitro and in mice as well as in human SGs and that PIP misexpression correlates with an altered AQP5 distribution at the acinar apical membrane in PIP knockout mice and SS hMSG. Furthermore, our data show that the protein-protein interaction involves the AQP5 C-terminus and the N-terminal of PIP (one molecule of PIP per AQP5 tetramer). In conclusion, our findings highlight for the first time the role of PIP as a protein controlling AQP5 localization in human salivary glands but extend beyond due to the PIP-AQP5 interaction described in lung and breast cancers