靶向PCSK9基因，真能一劳永逸降血脂？

Core Viewpoint - A new study published in Nature Medicine introduces a targeted epigenetic editor (PCSK9-EE) that significantly and sustainably lowers low-density lipoprotein cholesterol (LDL-C) levels in transgenic mice and crabs monkeys, raising hopes for lifelong lipid reduction in hyperlipidemia patients [1][6]. Group 1: Research Findings - The PCSK9-EE can almost completely suppress PCSK9 levels in the bloodstream of transgenic mice for at least one year after a single administration, while in crabs monkeys, it can reduce PCSK9 protein levels by approximately 90% and LDL-C levels by up to 70% for at least three months [5]. - PCSK9-EE operates through epigenetic modification of DNA methylation, silencing the expression of the PCSK9 gene in the liver, thus lowering LDL-C levels [4]. Group 2: Health Implications - Cardiovascular diseases, including coronary heart disease and stroke, are closely linked to elevated LDL-C levels, which have risen in global health risk rankings from the 14th to the 8th position between 1990 and 2019 [2]. - Factors contributing to high LDL-C levels include poor lifestyle choices, genetic predisposition, and age-related changes, which increase the risk of cardiovascular diseases [3]. Group 3: Current Treatment Landscape - Traditional lipid-lowering medications, primarily statins, have limitations, including inadequate LDL-C level control and potential side effects like muscle pain and elevated liver enzymes [4]. - Newer PCSK9 inhibitors have shown significant advantages in lipid management and are already in clinical use in China, with options for less frequent dosing [4]. Group 4: Future Considerations - Despite promising animal study results, PCSK9-EE has not yet entered clinical trials, and its long-term efficacy and safety in humans remain to be validated [6][7]. - The potential for PCSK9-EE to achieve "lifelong lipid reduction" is considered premature, with experts suggesting a more cautious interpretation of its benefits until further research is conducted [6][7].