Evidence suggests cholesterol accumulation in pro-inflammatory endothelial cells (EC) contributes to triggering atherogenesis and driving atherosclerosis progression. Therefore, inhibiting miR-33a-5p within inflamed endothelium may prevent and treat atherosclerosis by enhancing apoAI-mediated cholesterol efflux by upregulating ABCA1. However, it is not entirely elucidated whether inhibition of miR-33a-5p in pro-inflammatory EC is capable of increasing ABCA1-dependent cholesterol efflux. In our study, we initially transfected LPS-challenged, immortalized mouse aortic EC (iMAEC) with either pAntimiR33a5p plasmid DNA or the control plasmid, pScr. We detected significant increases in both ABCA1 protein expression and apoAI-mediated cholesterol efflux in iMAEC transfected with pAntimiR33a5p when compared to iMAEC transfected with pScr. We subsequently used polymersomes targeting inflamed endothelium to deliver either pAntimiR33a5p or pScr to cultured iMAEC and showed that the polymersomes were selective in targeting pro-inflammatory iMAEC. Moreover, when we exposed LPS-challenged iMAEC to these polymersomes, we observed a significant decrease in miR-33a-5p expression in iMAEC incubated with polymersomes containing pAntimR33a5p versus control iMAEC. We also detected non-significant increases in both ABCA1 protein and apoAI-mediated cholesterol in iMAEC exposed to polymersomes containing pAntimR33a5p when compared to control iMAEC. Based on our results, inhibiting miR-33a-5p in pro-inflammatory EC exhibits atheroprotective effects, and so precisely delivering anti-miR-33a-5p to these cells is a promising anti-atherogenic strategy.

This tutorial describes methods of characterizing nanomaterials in whole blood, and the associated benefits and shortcomings of each technique.

Abstract Many biological questions can benefit from the diverse perspectives of multiple disciplines, including engineering. In the last several decades, biological research has been advanced from engineering approaches to delineate processes including stem cell differentiation, optimizing cancer therapies, and building physical and genetic tools to manipulate cell function. The collaboration between fields necessitates a common language to bridge concepts that have historically been developed for engineering and emergent properties of biological systems. By utilizing the expertise of both fields, greater advances can be reached in biological research through the application of large data sets and modelling of biological processes. Parallels between cellular signalling and engineering process controls include feedback and feed‐forward loops, amplification and thresholds; in both fields, these subprocesses contribute widely to the overall function of the cell and engineered system. Feedback and feed‐forward loops, amplification and thresholds, along with their importance in biology and process controls and their contributions to overall function. Key Concepts Parallels exist between the structure and function of cellular signal transduction architectures and engineering process control concepts. Disruptions in signalling pathways and process control systems can have detrimental consequences, including health disorders and manufacturing casualties, respectively. Understanding cell signalling mechanisms in a process control context can provide a novel perspective for understanding treatments and therapies of diseases stemming from dysregulation of cellular controls. Similarities between everyday process controls like air conditioning can help unravel apparent complexities in cellular signaling. Using extended analogy between process controls and cellular signaling may provide insights into mechanisms of manipulation not previously explored.