Endothelial Dysfunction in Patients with Severe Mitral Regurgitation

Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. It has been reported that MVP patients-candidates for mitral valve repair (MVRep)-showed an alteration in the antioxidant defense systems as well as in the L-arginine metabolic pathway. In this study, we investigate if oxidative stress and endothelial dysfunction are an MVP consequence or driving factors. Forty-five patients undergoing MVRep were evaluated before and 6 months post surgery and compared to 29 controls. Oxidized (GSSG) and reduced (GSH) forms of glutathione, and L-arginine metabolic pathway were analyzed using liquid chromatography-tandem mass spectrometry methods while osteoprotegerin (OPG) through the ELISA kit and circulating endothelial microparticles (EMP) by flow cytometry. Six-month post surgery, in MVP patients, the GSSG/GSH ratio decreased while symmetric and asymmetric dimethylarginines levels remained comparable to the baseline. Conversely, OPG levels significantly increased when compared to their baseline. Finally, pre-MVRep EMP levels were significantly higher in patients than in controls and did not change post surgery. Overall, these results highlight that MVRep completely restores the increased oxidative stress levels, as evidenced in MVP patients. Conversely, no amelioration of endothelial dysfunction was evidenced after surgery. Thus, therapies aimed to restore a proper endothelial function before and after surgical repair could benefit MVP patients

Aortic valve sclerosis adds to prediction of short-term mortality in patients with documented coronary atherosclerosis

Aims: Aortic valve sclerosis (AVSc), a non-uniform thickening of leaflets with an unrestricted opening, is characterized by inflammation, lipoprotein deposition, and matrix degradation. In the general population, AVSc predicts long-term cardiovascular mortality (+50%) even after adjustment for vascular risk factors and clinical atherosclerosis. We have hypothesized that AVSc is a risk-multiplier able to predict even short-term mortality. To address this issue, we retrospectively analyzed 90-day mortality of all patients who underwent isolated coronary artery bypass grafting (CABG) at Centro Cardiologico Monzino over a ten-year period (2006\u20132016). Methods: We analyzed 2246 patients and 90-day all-cause mortality was 1.5% (31 deaths). We selected only patients deceased from cardiac causes (n = 29) and compared to alive patients (n = 2215). A cardiologist classified the aortic valve as no-AVSc (n = 1352) or AVSc (n = 892). Cox linear regression and integrated discrimination improvement (IDI) analyses were used to evaluate AVSc in predicting 90-day mortality. Results: AVSc 90-day survival (97.6%) was lower than in no-AVSc (99.4%; p < 0.0001) with a hazard ratio (HR) of 4.0 (95%CI: 1.78, 9.05; p < 0.0001). The HR for AVSc, adjusted for propensity score, was 2.7 (95%CI: 1.17, 6.23; p = 0.02) and IDI statistics confirmed that AVSc significantly adds (p < 0.001) to the identification of high-risk patients than EuroSCORE II alone. Conclusion: Our data supports the hypothesis that a risk stratification strategy based on AVSc, added to ESII, may allow better recognition of patients at high-risk of short-term mortality after isolated surgical myocardial revascularization. Results from this study warrant further confirmation

MATRIX METALLOPROTEINASES IN PRO-ATHEROSCLEROTIC ARTERIAL REMODELING

Matrix metalloproteinases (MMPs) is a family of Zn2+ endopeptidases that process various components of the extracellular matrix. These enzymes are also involved in activation and inhibition of signaling cascades through proteolytic cleavage of surface receptors. Moreover, MMPs play a key role in tissue remodeling and and repair. Dysregulation of MMPs is observed in patholofgical conditions, including atherosclerosis, which is associated with hyperactivation of MMPs, aberrant tissue remodeling and neovascularization of the growing atherosclerotic plaques. This makes MMPs interesting therapeutic targets that can be employed for developing novel therapies to treat atherosclerosis and its complications. Currently, a growing number of synthetic MMP inhibitors is available. In this review, we will discuss the role of these enzymes in atherosclerosis pathology and the ways of their pothential therapeutic use. © 2018 Elsevier Lt

Sialidase activity in human pathologies

Sialic acid residues are frequently located at the terminal positions of glycoconjugate chains of cellular glycocalyx. Sialidases, or neuraminidases, catalyse removal of these residues thereby modulating various normal and pathological cellular activities. Recent studies have revealed the involvement of sialidases in a wide range of human disorders, including neurodegenerative disorders, cancers, infectious diseases and cardiovascular diseases. The accumulating data make sialidases an interesting potential therapeutic target. Modulating the activity of these enzymes may have beneficial effects in several pathologies. Four types of mammalian sialidases have been described: NEU1, NEU2, NEU3 and NEU4. They are encoded by different genes and characterized by different subcellular localization. In this review, we will summarize the current knowledge on the roles of different sialidases in pathological conditions

New biomarkers for diagnosis and prognosis of localized prostate cancer

The diagnostics and management of localized prostate cancer is complicated because of cancer heterogeneity and differentiated progression in various subgroups of patients. As a prostate cancer biomarker, FDA-approved detection assay for serum prostate specific antigen (PSA) and its derivatives are not potent enough to diagnose prostate cancer, especially high-grade disease (Gleason ≥7). To date, a collection of new biomarkers was developed. Some of these markers are superior for primary screening while others are particularly helpful for cancer risk stratification, detection of high-grade cancer, and prediction of adverse events. Two of those markers such as proPSA (a part of the Prostate Health Index (PHI)) and prostate specific antigen 3 (PCA3) (a part of the PCA3 Progensa test) were recently approved by FDA for clinical use. Other markers are not PDA-approved yet but are available from Clinical Laboratory Improvement Amendment (CLIA)-certified clinical laboratories. In this review, we characterize diagnostic performance of these markers and their diagnostic and prognostic utility for prostate cancer. © 2018 Elsevier Lt

Potential of anti-inflammatory agents for treatment of atherosclerosis

Chronic inflammation is a central pathogenic mechanism of atherosclerosis induction and progression. Vascular inflammation is associated with accelerated onset of late atherosclerosis complications. Atherosclerosis-related inflammation is mediated by a complex cocktail of pro-inflammatory cytokines, chemokines, bioactive lipids, and adhesion molecules, and blocking the key pro-atherogenic inflammatory mechanisms can be beneficial for treatment of atherosclerosis. Therapeutic agents that specifically target some of the atherosclerosis-related inflammatory mechanisms have been evaluated in preclinical and clinical studies. The most promising anti-inflammatory compounds for treatment of atherosclerosis include non-specific anti-inflammatory drugs, phospholipase inhibitors, blockers of major inflammatory cytokines, leukotrienes, adhesion molecules, and pro inflammatory signaling pathways, such as CCL2-CCR2 axis or p38 MAPK pathway. Ongoing studies attempt evaluating therapeutic utility of these anti-inflammatory drugs for treatment of atherosclerosis. The obtained results are important for our understanding of atherosclerosis-related inflammatory mechanisms and for designing randomized controlled studies assessing the effect of specific anti-inflammatory strategies on cardiovascular outcomes