An Early Study on the Mechanisms that Allow Tissue-Engineered Vascular Grafts to Resist Intimal Hyperplasia

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study. Intimal hyperplasia in the outflow vein of TEVGs was assessed at the anastomosis and at juxta-anastomotic regions via histological analysis, and was compared to intimal hyperplasia with polytetrafluoroethylene (PTFE) grafts in the baboon model and in literature reports from other animal models. Less venous intimal hyperplasia was observed in histological sections with arteriovenous TEVGs than with arteriovenous PTFE grafts. TEVGs were associated with a mild, noninflammatory intimal hyperplasia. The extent of intimal tissue that formed with TEVG placement correlated with the rate of blood flow through tissue engineered vascular grafts at 2 weeks postimplant. Outflow vein dilatation was observed with increased flow rate. Both mid-graft flow rates and outflow vein diameters reached a plateau by week 4, which suggested that venous remodeling and intimal hyperplasia largely occurred within the first 4 weeks of implant in the baboon model. Given their compliant and noninflammatory nature, TEVGs appear resistant to triggers for venous intimal hyperplasia that are common for PTFE arteriovenous grafts, including (1) abundant proinflammatory macrophage populations that are associated with PTFE grafts and (2) compliance mismatch between PTFE grafts and the outflow vein. Our findings suggest that arteriovenous TEVGs develop only a mild form of venous intimal hyperplasia, which results from the typical hemodynamic changes that are associated with arteriovenous settings

Styrene maleic acid recovers proteins from mammalian cells and tissues while avoiding significant cell death.

Detection of protein biomarkers is an important tool for medical diagnostics, typically exploiting concentration of particular biomarkers or biomarker release from tissues. We sought to establish whether proteins not normally released by living cells can be extracted without harming cells, with a view to extending this into biomarker harvest for medical diagnosis and other applications. Styrene maleic acid (SMA) is a polymer that extracts nanodiscs of biological membranes (containing membrane proteins) from cells. Hitherto it has been used to harvest SMA-lipid-membrane protein particles (SMALP) for biochemical study, by destroying the living cellular specimen. In this study, we applied SMA at low concentration to human primary cardiovascular cells and rat vascular tissue, to 'biopsy' cell proteins while avoiding significant reductions in cell viability. SMA at 6.25 parts per million harvested proteins from cells and tissues without causing significant release of cytosolic dye (calcein) or reduction in cell viability at 24 and 72 hours post-SMA (MTT assay). A wide range of proteins were recovered (20-200 kDa) and a number identified by mass spectrometry: this confirmed protein recovery from plasma membrane, intracellular membranes and cell cytosol without associated cell death. These data demonstrate the feasibility of non-lethally sampling proteins from cells, greatly extending our sampling capability, which could yield new physiological and/or pathological biomarkers

Distinct Impact of Three Different Statins on Arteriovenous Fistula Outcomes: A Retrospective Analysis

Whether statins improve arteriovenous fistula (AVF) outcomes is still a matter of debate. Taking into consideration the existing physicochemical differences between individual drugs, this study evaluates the impact of three different statins (atorvastatin, rosuvastatin and simvastatin) on one-stage and two-stage AVF outcomes. Using a retrospective cohort of 535 patients, we analyzed the effects of each statin on primary failure and primary patency using multivariate logistic regressions and Cox proportional hazard models. Out of the three statins analyzed, only atorvastatin improved the overall primary failure of AVF (odds ratio [OR] = 0.18, p = 0.005). Comparisons between the two AVF types demonstrated that this effect was due to a prominent reduction in primary failure of one-stage (OR = 0.03; p = 0.005), but not two-stage fistulas (OR = 0.43; p = 0.25). In contrast, primary patency of two-stage (hazards ratio [HR] = 0.51; p = 0.024), but not one-stage fistulas (HR = 0.98; p = 0.95), was improved by all statins as a group, but not by individual drugs. Our results suggest that the potential benefit of statins on AVF outcomes is a drug-specific and not a class effect, and that such effect is also influenced by the type of fistula