Dyslipidemia drives atherosclerosis: it requires mechanistic research, emerging therapies, precision strategies, combined with guidelines and technologies to optimize prevention and treatment.
Review Article
Dyslipidemia drives atherosclerosis: it requires mechanistic research, emerging therapies, precision strategies, combined with guidelines and technologies to optimize prevention and treatment.
Dyslipidemia is a central driver in the initiation and progression of atherosclerosis (AS). The chronic inflammation and endothelial injury triggered by dyslipidemia are key pathological events in AS development. Elucidating the molecular network underlying dyslipidemia and developing precise interventions are critical for achieving precision prevention and treatment of AS. Recent studies have demonstrated that sterol regulatory element-binding protein 1 (SREBP1) and lipoprotein(a) [Lp(a)] play pivotal roles in the regulation of lipid synthesis and transport. Additionally, gut microbiota-derived metabolites, such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can activate inflammatory pathways and promote lipid deposition via inter-organ signaling axes, thereby accelerating the progression of AS.
However, clinical studies have revealed that even when low-density lipoprotein cholesterol (LDL-C) levels are within the recommended range, a significant number of patients continue to experience cardiovascular events. This indicates the widespread presence of "residual risk". Such residual risk is primarily driven by elevated non-high-density lipoprotein cholesterol (non-HDL-C), abnormal levels of Lp(a), and imbalances in the triglyceride to HDL-C (TG/HDL-C) ratio, highlighting the limitations of traditional therapies in comprehensive lipid profile management.
Emerging targeted therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, small interfering RNA (siRNA)-based treatments, and Lp(a)-lowering agents like pelacarsen, represent promising strategies for more precise lipid modulation.
With the continuous advancement of related research, the precise management of AS will increasingly rely on deeper mechanistic insights and individualized therapeutic strategies. Current strategies for AS prevention and treatment focus on understanding key pathways, including lipid metabolism, inflammation, and vascular dysfunction, to develop targeted therapies. The integration of the 2023 Chinese Guidelines for Lipid Management, imaging, and AI-assisted decision-making will promote data-driven, precision medicine. Personalized drug selection, efficacy monitoring, and long-term follow-up will optimize clinical outcomes and enhance prevention strategies for high-risk patients.
Atherosclerosis (AS) is the primary pathological basis of cardiovascular diseases and is fundamentally recognized as a chronic inflammatory condition1. It leads to arterial narrowing or even occlusion, ultimately resulting in atherosclerotic cardiovascular diseases (ASCVD) such as coronary artery disease (CAD) and stroke2,3. According to global estimates, approximately 17.6 million deaths annually are attributed to ASCVD4. In China alone, the total number of ASCVD patients has reached 330 million, including 11.39 million individuals diagnosed with CAD, with the p....
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Core Pathological Mechanisms of As:
Key transcription factors in lipid metabolism
A hallmark of AS is abnormal lipid accumulation in the arterial wall, closely linked to dysregulated transcriptional control of lipid metabolism, including cholesterol and fatty acid metabolism. Key regulators like liver X receptors (LXRs), peroxisome proliferator-activated receptors (PPARs), and SREBPs control lipid homeostasis. Dysfunction of these transcription factors can directly contribute to lipid metabolic disorders, promoting AS progression.
Liver X receptors (LXRs)
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Dysregulation of lipid metabolism is closely associated with the initiation and progression of atherosclerosis (AS), and dyslipidemia remains one of the most modifiable risk factors for this condition. This review has outlined the molecular mechanisms underlying AS, key targets involved in lipid abnormalities, and diverse clinical intervention strategies. Current research highlights the pivotal roles of gene regulation (e.g., SREBP1, LPA) and epigenetic pathways (e.g., ABCA1-seRNA, mTORC1.......
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The authors declare that they have no conflicts of interest. The authors disclose using an artificial intelligence language model (ChatGPT) only for language polishing in preparing this review manuscript. All outputs were thoroughly reviewed and edited by the authors. ChatGPT was strictly confined to improving linguistic clarity and expression, without involvement in idea generation, data analysis, interpretation, or conclusion drafting. The authors conducted all literature citations, evidence synthesis, and conclusions independently based on the referenced studies, ensuring both accuracy and compliance with academic standards. Thus, the use of ChatGPT was limited solely to language optimization, while the scientific content and intellectual contribution remain entirely the responsibility of the authors.
The authors declare they have no funding or financial support for this work.
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