Atherosclerosis is the primary process that underlies cardiovascular disease. The connection between LDL cholesterol and the formation of atherosclerotic plaques is established by solid evidence. PCSK9 inhibitors have proven to be a valuable and practical resource for lowering the LDL cholesterol of many patients in recent years. Their inhibitory effect on atherosclerosis progression seems to be driven not just by lipid metabolism modification but also by LDL-independent mechanisms. We review the effect of PCSK9 inhibitors on various mechanisms involving platelet activation, inflammation, endothelial dysfunction, and the resultant clot formation. The main effectors of PCSK9 activation of platelets are CD36 receptors, lipoprotein(a), oxidised LDL particles, tissue factor, and factor VIII. Many more molecules are under investigation, and this area of research is growing rapidly.
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http://dx.doi.org/10.3390/ph16091197 | DOI Listing |
Clin Nutr ESPEN
January 2025
Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal; Laboratório Associado para a Sustentabilidade e Tecnologia em Regiões de Montanha (SusTEC), Instituto Politécnico de Bragança, Campus de Santa Apolónia, 5300-253 Bragança, Portugal. Electronic address:
Background: Dyslipidaemia is among the major causes of severe diseases and, despite being well-established, the hypocholesterolaemic therapies still face significant concerns about potential side effects (such as myopathy, myalgia, liver injury digestive problems, or mental fuzziness in some people taking statins), interaction with other drugs or specific foods. Accordingly, this review describes the latest developments in the most effective therapies to control and regulate dyslipidaemia.
Scope And Approach: Herein, the metabolic dynamics of cholesterol and their integration with the current therapies: statins, bile acid sequestrants, fibrates, niacin, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, reconstituted high-density lipoprotein (rHDL), or anti-inflammatory and immune-modulating therapies), were compared focusing their effectiveness, patients' adhesion and typical side-effects.
Acta Physiol (Oxf)
February 2025
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally, with elevated low-density lipoprotein cholesterol (LDL-C) levels being a major risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating LDL-C levels by promoting the degradation of hepatic low-density lipoprotein receptors (LDLR) responsible for clearing LDL-C from the circulation. PCSK9 inhibitors are novel lipid-modifying agents that have demonstrated remarkable efficacy in reducing plasma LDL-C levels and decreasing the incidence of CVD.
View Article and Find Full Text PDFCardiovasc Diagn Ther
December 2024
Department of Cardiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Engineering Research Center of Cardiovascular Wisdom Diagnosis and Treatment, Beijing, China.
Background: The prevalence of very high-risk atherosclerotic cardiovascular disease (ASCVD) is significant in China, with suboptimal rates of low-density lipoprotein cholesterol (LDL-C) compliance exacerbating plaque instability and causing a higher incidence of major adverse cardiac events (MACEs). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are effective in reducing LDL-C levels, increase the stability of vulnerable plaque, and influence the progression of atherosclerosis through multiple mechanisms as demonstrated in animal studies. However, there is currently a lack of evidence regarding the efficacy and safety of high-intensity statin therapy combined with PCSK9i in the secondary prevention of ASCVD in the Chinese population.
View Article and Find Full Text PDFCurr Atheroscler Rep
January 2025
Unitat de Medicina Vascular I Metabolismo, Hospital Universitario Sant Joan, Universitat Rovira I Virgili, IISPV, CIBERDEM, Reus, Spain.
Purpose Of The Review: A significant number of patients fail to achieve target LDL cholesterol (LDL-C) levels. This review aims to explore why inclisiran, a novel class of LLT, should be considered a valuable addition to the current treatment options.
Recent Findings: Inclisiran is a small interfering RNA (siRNA) that targets PCSK9 synthesis specifically in the hepatocytes.
Int J Med Sci
January 2025
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, People's Republic of China.
Elevated lipoprotein(a) [Lp(a)] levels are increasingly recognized as a significant risk factor for cardiovascular diseases and may also contribute to atrial fibrillation (AF). This review investigated the indirect mechanisms through which Lp(a) may influence AF, including proatherogenic, prothrombotic, and proinflammatory pathways. Traditional lipid-lowering therapies, such as lifestyle modifications and statins, have limited effects on Lp(a) levels.
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