1. (10 pts) What was the broad human health motivation for this study? What was the specific scientific motivation for this study?
The overall motivation was to reduce the risk of coronary artery diseases(CAD) by finding a relation between lymphatic system and reduction of LDL- cholesterol from the blood and to design new generation therapeutic for atherosclerosis using PCSK-9. The scientific motivation of the study is to characterize the source of lymphatic dysfunction related to atherosclerosis by inhibiting PCSK-9 in the mouse model.

2. (10 pts) What was the major objective of this study?
Lymphatic dysfunction is proved to cause atherosclerosis, but number of mechanism and pathways are involved in the process. LDL cholesterol needs to …show more content…
These models are prone increased inflammatory and oxidative stress conditions so that can be used to induce atherosclerosis much easier. In this figure 5 the mice model developed atherosclerotic lesions as early as four months because of that the author decided to check influence of the lymphatic system vessels at 3 months. The results showed that there was no significant different between the affected and the control mice up to 12 months after which the condition worsens in the ldlr -/- and hApoB100 +/+ model mice. From this result it was clear that the initial lymphatic dysfunction was not responsible for inducing the atherosclerosis, but it suggests that after the time progress the condition worse and it was clear that this was age dependent …show more content…
This is mechanism which keeps the total body cholesterol under control. During this process apolipoprotein APOA1 (pre-βHDL) eliminates the cholesterol and send to liver for excretion. New studies show that lymphatic vessels play an essential role in reverse cholesterol transport mechanism4. This mechanism can be further studied, and new line of therapeutic drugs can be created which reduces ASCAD

Reference
1) Milasan, A., Dallaire, F., Mayer, G., & Martel, C. (2016). Effects of LDL Receptor Modulation on Lymphatic Function. Scientific Reports, 6(1). doi:10.1038/srep27862
2) Mishra, S., Somvanshi, P. R., & Venkatesh, K. V. (2014). Control of cholesterol homeostasis by entero-hepatic bile transport – the role of feedback mechanisms. RSC Adv.,4(103), 58964-58975. doi:10.1039/c4ra09397f
3) Rashid, S. et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proceedings of the National Academy of Sciences of the United States of America 102, 5374–5379, doi: 10.1073/pnas.0501652102