RESUMEN
The proprotein convertase subtilisin/kexin type 9 (PCSK9) acts via a canonical pathway to regulate circulating low-density lipoprotein-cholesterol (LDL-C) via degradation of the LDL receptor (LDLR) on the liver cell surface. Published research has shown that PCSK9 is involved in atherosclerosis via a variety of non-classical mechanisms that involve lysosomal, inflammatory, apoptotic, mitochondrial, and immune pathways. In this review paper, we summarized these additional mechanisms and described how anti-PCSK9 therapy exerts effects through these mechanisms. These additional pathways further illustrate the regulatory role of PCSK9 in atherosclerosis and offer an in-depth interpretation of how the PCSK9 inhibitor exerts effects on the treatment of atherosclerosis.
Asunto(s)
Aterosclerosis/enzimología , LDL-Colesterol/sangre , Diabetes Mellitus/enzimología , Dislipidemias/enzimología , Inflamación/enzimología , Proproteína Convertasa 9/metabolismo , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticolesterolemiantes/uso terapéutico , Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patología , Diabetes Mellitus/sangre , Diabetes Mellitus/patología , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/patología , Células Endoteliales/enzimología , Células Endoteliales/patología , Humanos , Inflamación/sangre , Inflamación/patología , Macrófagos/enzimología , Macrófagos/patología , Inhibidores de PCSK9 , Placa Aterosclerótica , Inhibidores de Serina Proteinasa/uso terapéuticoRESUMEN
AIMS: The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD). METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words "methotrexate," "cardiovascular," "acute coronary syndrome," "coronary heart disease," "myocardial infarction," "angina pectoris," and "rheumatoid arthritis." The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death. RESULTS: A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726-0.876, Pâ=â.001, I2â=â27. 9%). CONCLUSION: MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.