Unlocking the mysteries of VLDL: exploring its production, intracellular trafficking, and metabolism as therapeutic targets

Author:

Chen Jingfei,Fang Zhenfei,Luo Qin,Wang Xiao,Warda Mohamad,Das Avash,Oldoni Federico,Luo Fei

Abstract

AbstractReducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.

Funder

National Natural Science Foundation of China

Hunan Provincial Natural Science Foundation of China

Scientific Research Project of Hunan Provincial Health Commission

Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University

China Postdoctoral Science Foundation

Key Research and Development Program of Hunan Province of China

Publisher

Springer Science and Business Media LLC

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