Inhibition of proprotein convertase subtilisin/kexin type 9 in the treatment of hypercholesterolemia.
نویسنده
چکیده
Según datos de la Organización Mundial de la Salud, la enfermedad cardiovascular de origen isquémico o arterioscleroso (ECVA) es la primera causa de muerte en el mundo y especialmente en los países desarrollados. La aterosclerosis es una enfermedad arterial multifactorial, en la que el depósito en el espacio subendotelial de las lipoproteínas que transportan apolipoproteína B y colesterol, principalmente las lipoproteínas de baja densidad (LDL), y los fenómenos inflamatorios y proliferativos que posteriormente se desarrollan son fundamentales en el desarrollo y en las manifestaciones clínicas de la ECVA. Por consiguiente, la aterosclerosis es una enfermedad «colesterol dependiente», iniciada por el depósito de colesterol en la íntima arterial. La reducción de las concentraciones del colesterol de las LDL (cLDL) es el principal objetivo de las estrategias para prevenir o tratar la ECVA. El tratamiento con estatinas, inhibidores de la 3-hidroxi-3-metil-glutaril-CoA reductasa, capaces de reducir entre un 30-50% las concentraciones de cLDL, han demostrado beneficios en la reducción de la enfermedad cardiovascular y son consideradas por todas las sociedades científicas y todas las guías como el primer escalón terapéutico por su eficacia en la reducción de cLDL y el riesgo de ECVA, con una reducción de episodios cardiovasculares mayores de un 21% por cada 39 mg/dl de descenso en los valores de cLDL. Estos resultados son independientes del
منابع مشابه
Anti-PCSK9 antibodies for the treatment of heterozygous familial hypercholesterolemia: patient selection and perspectives
Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels from birth, which exposes the arteries to high levels of atherogenic lipoproteins lifelong and results in a significantly increased risk of premature cardiovascular events. The diagnosis of FH, followed by an appropriate and early treatment is critical to reduce...
متن کاملProprotein convertase subtilisin/kexin type 9 enzyme inhibitors: An emerging new therapeutic option for the treatment of dyslipidemia
The treatment of hypercholesterolemia entered in a new phase of development with the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the market. The Food and Drug Administration and European Medicines Agency recently approved the alirocumab and evolocumab, subcutaneously injectable monoclonal antibody every 2 or 4 weeks against PCSK9, for the treatment of hyp...
متن کاملQuercetin-3-glucoside increases low-density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture
Low-density lipoprotein receptor (LDLR) mediates hepatic clearance of plasma cholesterol; proprotein convertase subtilisin/kexin 9 (PCSK9) opposes this clearance by promoting LDLR degradation. The plant flavonoid quercetin-3-β-d-glucoside (Q3G) has been shown to reduce hypercholesterolemia in experimental animals. Here, we examined how it affects LDLR and PCSK9 expression as well as LDL uptake ...
متن کاملProprotein convertase subtilisin/kexin type 9 (PCSK9): lessons learned from patients with hypercholesterolemia.
BACKGROUND Identification of the proprotein convertase subtilisin/kexin type 9 (PCSK9) as the third gene causing familial hypercholesterolemia (FH) and understanding its complex biology has led to the discovery of a novel class of therapeutic agents. CONTENT PCSK9 undergoes autocatalytic cleavage in the endoplasmic reticulum and enters the secretory pathway. The PCSK9 gene is under the regula...
متن کاملCirculating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue.
OBJECTIVE Proprotein convertase subtilisin/kexin 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptor (LDLR), and its gene is the third locus implicated in familial hypercholesterolemia. Herein, we investigated the role of PCSK9 in adipose tissue metabolism. METHODS AND RESULTS At 6 months of age, Pcsk9(-/-) mice accumulated ≈80% more visceral adipose tissue than wild-ty...
متن کاملDevelopment of proprotein convertase subtilisin/kexin type 9 inhibitors and the clinical potential of monoclonal antibodies in the management of lipid disorders
The aim of this manuscript is to review available data to evaluate the present status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed. The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein cholesterol and other atherogenic lipid fractions was studied in various Phase 2 an...
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ورودعنوان ژورنال:
- Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion
دوره 63 6 شماره
صفحات -
تاریخ انتشار 2016