👤 Konstantinos A Papathanasiou

Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease, and it is particularly associated with premature acute coronary syndrome (ACS). We investigated whether elevated Lp(a) can predict recurrent cardiovascular events in patients who experienced their first ACS less than or equal to 40 years of age. Within the STudy of eArly Myocardial INfArction registry, we recruited 405 consecutive patients who survived their first ACS less than or equal to 40 years of age; of them 378 had complete follow-up data. Clinical endpoint was the development of major adverse cardiovascular events (MACE; i.e. cardiac death, readmission for ACS or malignant ventricular arrhythmias, ischemic stroke, or coronary revascularization due to clinical deterioration). Multi-adjusted Cox regression was used to assess the association between Lp(a) and first recurrent MACE risk. Of the 378 ACS survivors (33.7 ± 4.3 years), 139 (36.8%) experienced a MACE over a median 8-year (5.2-12.5 years) follow-up. Elevated Lp(a) showed a borderline independent association with higher recurrent MACE [hazard ratio per 1 mg/dl: 1.004, 95% confidence interval (CI): 0.999-1.009, P = 0.051]. Moreover, patients with baseline Lp(a) levels greater than or equal to 50 mg/dl had 82.6% higher risk of MACE as compared with those below (hazard ratio 1.826, 95% CI: 1.141-2.925, P = 0.012); similarly, patients with Lp(a) ≥ 70 mg/dl had 118% higher risk as compared with those below (hazard ratio 2.180, 95% CI: 1.330-3.573, P = 0.002). Elevated Lp(a) concentrations demonstrate an independent association with recurrent MACE among very young ACS survivors. Until targeted Lp(a)-lowering treatments become clinically available, an aggressive lipid-lowering approach may be warranted to partially attenuate Lp(a)-related residual cardiovascular risk. Show less

Osteoarthritis (OA) is a multi-factorial disease leading progressively to loss of articular cartilage and subsequently to loss of joint function. While hypertrophy of chondrocytes is a physiological process implicated in the longitudinal growth of long bones, hypertrophy-like alterations in chondrocytes play a major role in OA. We performed a quantitative proteomic analysis in osteoarthritic and normal chondrocytes followed by functional analyses to investigate proteome changes and molecular pathways involved in OA pathogenesis. Chondrocytes were isolated from articular cartilage of ten patients with primary OA undergoing knee replacement surgery and six normal donors undergoing fracture repair surgery without history of joint disease and no OA clinical manifestations. We analyzed the proteome of chondrocytes using high resolution mass spectrometry and quantified it by label-free quantification and western blot analysis. We also used WebGestalt, a web-based enrichment tool for the functional annotation and pathway analysis of the differentially synthesized proteins, using the Wikipathways database. ClueGO, a Cytoscape plug-in, is also used to compare groups of proteins and to visualize the functionally organized Gene Ontology (GO) terms and pathways in the form of dynamical network structures. The proteomic analysis led to the identification of a total of ~2400 proteins. 269 of them showed differential synthesis levels between the two groups. Using functional annotation, we found that proteins belonging to pathways associated with regulation of the actin cytoskeleton, EGF/EGFR, TGF-β, MAPK signaling, integrin-mediated cell adhesion, and lipid metabolism were significantly enriched in the OA samples (p ≤10(-5)). We also observed that the proteins GSTP1, PLS3, MYOF, HSD17B12, PRDX2, APCS, PLA2G2A SERPINH1/HSP47 and MVP, show distinct synthesis levels, characteristic for OA or control chondrocytes. In this study we compared the quantitative changes in proteins synthesized in osteoarthritic compared to normal chondrocytes. We identified several pathways and proteins to be associated with OA chondrocytes. This study provides evidence for further testing on the molecular mechanism of the disease and also propose proteins as candidate markers of OA chondrocyte phenotype. Show less