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Targeting PCSK9 is an innovative approach in the fight against hyperlipidemia because it provides a specific and effective method to decrease LDL-C levels, reducing cardiovascular risk, and offering a valid alternative for individuals who may not respond well to or do not tolerate statins. The PCSK9 pathway is just one of several targets in the complex network of lipid metabolism. Combining PCSK9 inhibitors with other lipid-lowering agents may create synergistic effects, allowing for more comprehensive control of lipid levels. This research project aims at understanding the effect of statins treatment in hepatocarcinoma cells where the levels of PCSK9 will be downregulated via CRISPR-Cas9 genome editing. There are several studies both in vitro and in vivo, where the effect of different lipid-lowering drugs is evaluated in terms of reducing blood cholesterol levels and total levels of LDLs. Less frequent are the studies where the effect of PCSK9 inhibition is tested in combination with statin therapy. In this project we will evaluate if statins treatment and genome editing for PCSK9 will lead to an increased expression of LDL receptors in our hepatocarcinoma cell lines.

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