SUMMARY

Cardiovascular disease (CVD) remains as one of the most impactful diseases in the western hemisphere. Atherosclerosis, the underlying pathology for CVD, is the stiffening and occlusion of arteries that may ultimately cause heart attacks or strokes. While there are many therapeutic options available to treat the pathological symptoms, there is a large unmet need for synergistic approaches that actively address the regression of atherosclerosis rather than progression preventative focuses. MicroRNAs may help to address this need as short RNA sequences that play active roles in multiple disease pathways. In particular, inhibiting the microRNA mmu-miR-712 in atherosclerotic mice using am712 (am712) results in atherosclerotic plaque reduction. However, its effectiveness may benefit from the addition of a specific method of delivery to the target site. This study will screen for the in vitro effects of delivering am712 using targeted nanomaterials derived from high-density lipoproteins (HDL), which have been known to be an endogenous transporter of microRNAs through blood circulation. To do so involves the engineering of HDL-derived nanomaterials to incorporate am712 (HDL-am712), the implementation of a microfluidic device to mimic and screen HDL-am712 effects on the inflamed endothelium in vitro, and the in vivo validation of the findings with a mouse model.