Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy with EDTA- and PGG-Loaded Nanoparticles

One particularly important issue facing the medical and research community focused on cardiovascular health is the formation and rupture of abdominal aortic aneurysms (AAA). This is largely because, should an AAA rupture, the survival rate is very low -about 10-15 percent. Understanding what leads to the formation of these aneurysms is a critical first step in the search for a safe and effective treatment. Fortunately, after years of dedicated research, one of the primary causes of AAA has been determined to be calcification. Current treatments that have had success in animals rely on pretreatment of the aneurysm. Since over 90 percent of the patients are diagnosed with aneurysms in a moderate stage of development, it is important to find a treatment that can be effective after the aneurysm has already formed. One such treatment that has had success in rats is the application of calcium chloride to the infra-renal aorta. Additionally, previous research has shown that systematic delivery of elastin-antibody conjugated, poly (D,L-lactide) NPs loaded with hydroxamate-based MMP inhibitor batimastat (BB-94) causes suppression of AAA. However, these successes were based on trying to treat AAAs in the initial phases of their onset, not in moderate stages.

This was the main intention of the study conducted by Nosoudi et al. from Clemson University. By using targeted NPs-based delivery of EDTA to remove calcification deposits, and then using targeted delivery of PGG, a polyphenol found to stabilize elastin and increase elastic fiber deposition, the team hoped to be able to restore the elastic lamina in the aneurismal wall, causing an improvement in vascular elasticity. To be able to do this, the research team needed to properly measure the different enzymes that contribute to vascular elasticity, such as lysyl oxidase (LOX). They used the Amplite Fluorimetric Lysyl Oxidase Assay Kit to facilitate this, which uses Amplite's proprietary LOX substrate to releases hydrogen peroxide upon LOX oxidation, producing a sensitive fluorescent assay for an accurate and reliable reading of LOX activity.

What they found is that this treatment method does in fact have a noticeable impact on vascular elasticity. It helps to remove mineral deposits in the aortic wall, which in turn regenerates and restores elastic lamina. This indicates a new direction for treating AAA moving forward, and represents a groundbreaking development in understanding AAA. A study like this that promises new treatment options is not conclusive unless the tools used to conduct it are considered safe and reliable. Because the Amplite Fluorimetric Lysyl Oxidase Assay Kit uses an HRP substrate in the HRP-coupled reactions that can detect sub ng/ml LOX, it is much more sensitive than other assays designed for this enzyme activity. Thus, it is able to produce more accurate readings that can be depended on to make significant conclusions such as the one drawn from Nosudi's research. Further tests will need to be done to see if this method is effective on humans, but it offers great promise for treating an otherwise dangerous condition of the human heart.

References

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1. Nosoudi, Nasim, et al. "Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy with EDTA-and PGG-Loaded Nanoparticles." Theranostics 6.11 (2016): 1975.