This literature systematically reviews the role of PCSK9 in regulating low-density lipoprotein cholesterol metabolism and comprehensively summarizes research advances in PCSK9 inhibitors for cardiovascular disease treatment. It also discusses the performance of PCSK9 inhibitors with different administration routes in clinical trials and future development directions.
Literature Overview
This article, 'The discovery of PCSK9 as a pivotal point in the prevention of cardiovascular disease', published in the American Journal of Preventive Cardiology, reviews the role of PCSK9 protein in regulating low-density lipoprotein cholesterol (LDL-C) metabolism and provides detailed analysis of PCSK9 inhibitors (PCSK9i) for reducing atherosclerotic cardiovascular disease (ASCVD) risk. The article summarizes PCSK9i efficacy across different populations and evaluates their potential public health impact.
Background Knowledge
PCSK9 (proprotein convertase subtilisin-like 9) is a critical regulator of LDL receptor (LDLR) degradation. Its functional abnormalities are closely associated with familial hypercholesterolemia and related diseases. PCSK9 inhibition enhances LDLR recycling to reduce LDL-C levels. Current PCSK9i therapies include monoclonal antibodies (mAb), small interfering RNA (siRNA), oral inhibitors, and CRISPR/Cas9 gene-editing technologies, all demonstrating significant LDL-C reduction in clinical trials. However, their high costs and accessibility challenges limit widespread application. Additionally, emerging evidence suggests roles of PCSK9 in infection and inflammation, opening new research avenues. The article details PCSK9i applications across patient populations including ASCVD patients, heterozygous familial hypercholesterolemia (HeFH), and high-risk primary prevention groups, providing clinical practice guidance.
Research Methods and Experiments
The article systematically reviews PCSK9's biological functions and interaction mechanisms with LDLR, analyzing PCSK9 inhibitor efficacy across multiple randomized controlled trials (RCT). The research covers PCSK9 monoclonal antibodies (mAb), siRNA, oral inhibitors, and gene-editing therapies. It evaluates PCSK9i applications in different clinical settings including secondary prevention, primary prevention, and high-risk populations.
Key Conclusions and Perspectives
Research Significance and Prospects
PCSK9i hold significant clinical value for reducing ASCVD risk. Future development directions include oral formulations, gene-editing therapies, and in-depth studies targeting specific subpopulations (e.g., elevated Lp(a), mild aortic stenosis). The article emphasizes that broader adoption requires cost-control strategies and early combination therapy integration.
Conclusion
This article comprehensively reviews the central role of PCSK9 in lipid metabolism and systematically summarizes research advances regarding PCSK9 inhibitors in cardiovascular disease prevention. While PCSK9i demonstrate substantial LDL-C reduction in multiple RCTs, high costs and accessibility remain key implementation barriers. Future developments through alternative delivery methods (e.g., siRNA, oral formulations) and gene-editing technologies could expand their applications in high-risk patient populations. The article also highlights the need for further investigation into PCSK9i's potential roles in infection and inflammation regulation. Combined with current clinical guidelines and research trends, PCSK9i are expected to play critical roles in both primary and secondary ASCVD prevention.
