Novel strategies for decreasing cholesterol level based on PCSK9 molecular inhibitors

Cardiovascular diseases (CVD) remain the most common causes of death worldwide. Hyperlipidemia is a well-established risk factor for developing cardiovascular diseases. Proprotein convertase subtisiln kexin type 9 (PCSK9) is a serine protease involved in cholesterol homeostasis which causes the reduction of the number of LDLR in hepatocytes through promoting their metabolism and subsequent degradation. In addition, PCSK9 gain of function mutation is linked to familial hypercholesterolemia and premature CVD. Therefore inhibiting the function of PCSK9 is of great interest and today PCSK9 inhibitors are a novel class of cholesterol lowering drugs. microRNAs are an important group of biological regulators that suppress gene expression and are known to affect PCSK9 transcript level and function too. Identification of novel regulatory pathways of PCSK9 can help understanding the molecular mechanism of cholesterol homeostasis and lead to develop a new generation of drugs based on regulatory molecules like miRNAs.