Downstream coronary effects of drug-eluting stents.

BACKGROUND: Antiproliferative agents used in drug-eluting stents (DES) attenuate atherosclerosis, yet DES implantation has been linked to endothelial dysfunction. The downstream effects of DES on new lesion formation have not been previously directly examined. We sought to compare the development of de novo stenoses and need for treatment in the downstream coronary vessel of patients treated with DES or a bare-metal stent. METHODS: Angiographic images and procedural information were prospectively collected on 463 adults who underwent implantation of a single stent in a proximal coronary artery, had an appropriate control vessel for comparison, and subsequently returned for intervention. Propensity matching identified 89 pairs of patients. End points were defined as angiographic identification of a de novo stenosis or need for secondary intervention in the downstream vessel within 12 months of initial intervention. RESULTS: In the overall (P < .01) and propensity-matched cohort (P = .01), there was reduced risk of new lesions downstream to DES. No difference was seen in respective control vessels (P = .14 and P = .99). A reduced need for downstream intervention with DES was seen in both the overall (P = .01) and propensity-matched cohorts (P = .04). No difference was seen in the control vessels (P = .98 and P = .36). Multivariate proportional hazards modeling of known atherosclerosis risk factors identified stent type as the sole predictor for downstream lesions (P < .01) and downstream events (P = .02). CONCLUSIONS: Patients receiving DES appear less likely to develop downstream stenoses and events compared with patients receiving bare-metal stents, suggesting beneficial downstream drug delivery.

Engineering liver tissue spheroids with inverted colloidal crystal scaffolds.

Multicellular spheroids provide a new three-dimensional (3D) level of control over morphology and function of ex vivo cultured tissues. They also represent a valuable experimental technique for drug discovery and cell biology. Nevertheless, the dependence of many cellular processes on the cluster diameter remains unclear. To provide a tool for the systematic evaluation of such dependences, we introduce here inverted colloidal crystal (ICC) scaffolds. Uniformly sized pores in ICC cell matrixes afford a high yield production of controlled size spheroids in standard 96 well-plates. Transparent hydrogel matrix and ship-in-bottle effect also allows for convenient monitoring of cell processes by traditional optical techniques. Different developmental stages of 46.5-151.6 microm spheroids from HepG2 hepatocytes with vivid morphological similarities to liver tissue (bile canaliculi) were observed. The liver-specific functions of HepG2 cells were systematically investigated and compared for spheroids of different diameters as well as 2D cultures. Clear trends of albumin production and CYP450 activity were observed; diffusion processes and effect of cellular aggregation on metabolic activity were identified to be the primary contributors to the size dependence of the liver functions in HepG2 spheroids in ICC scaffolds. Since the aggregation of cells into clusters is a universal biological process, these findings and scaffolds can be applied to many other relevant cell types.