PCSK 9, un nuevo blanco terapéutico para el control de la hipercolesterolemia.PCSK 9, a new therapeutic target for the control of hypercholesterolemia. Roberto ResumenLa hipercolesterolemia es un importante factor de riesgo cardiovascular (ECV), que puede ser causada por factores genéticos, por llevar una vida sedentaria y malos hábitos alimenticios, teniendo como resultado elevados niveles de lípidos séricos, principalmente colesterol asociado a lipoproteínas de baja densidad (LDL-C). La dieta terapéutica, fármacos como ezetimiba y las estatinas son la principal estrategia utilizada para disminuir los niveles de LDL-C. Sin embargo, en un porcentaje de pacientes, estas medidas no logran una reducción de los niveles séricos LDL-C, principalmente por intolerancia a las estatinas o por causas genéticas de la hipercolesterolemia. La proproteína convertasa subtilisina/kexina tipo 9 (PCSK9), una serina proteasa recientemente caracterizada, ha surgido como un importante regulador del metabolismo del LDL-C, favoreciendo la degradación de su receptor (LDLR) en el lisosoma del hepatocito. Esto la convierte en un buen blanco terapéutico para controlar los niveles de LDL-C en pacientes hipercolesterolémicos, disminuyendo así el riesgo de desarrollar ECV. La estrategia en la que más se ha avanzado para controlar PCSK9 es a través de anticuerpos monoclonales anti-PCSK9. Se han realizado varios ensayos clínicos que muestran hasta el momento su efectividad en el control de LDL-C y bajo nivel de efectos adversos. Esta revisión muestra parte de esos estudios y los resultados que se han obtenido con el uso de este nuevo fármaco aún en desarrollo y que muestra un enorme potencial.Palabras clave: Enfermedades Cardiovasculares; Proproteína Convertasa 9; anticuerpos; Receptores de LDL. (Fuente: DeCS BIREME) AbstractHypercholesterolemia is produced not only by a sedentary lifestyle and nutritional disorders but also due to genetic factors that result in elevated serum lipids, mainly low-density lipoproteins associated cholesterol (LDL-C), contributing as a risk factor for the development of cardiovascular diseases. A therapeutic diet and statins are the first line strategies aimed to reduce the levels of LDL-C in hypercholesterolemic patients. Nevertheless, statins are not devoid of side effects, or a lack of efficiency in some patients. The proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine protease has been described recently to play an important role in the metabolism of LDL-C, favoring the degradation of its membrane receptor (LDLR) in the hepatocyte. This makes PCSK9 an excellent therapeutic target for the control of LDL-C in hypercholesterolemic patients, reducing their cardiovascular risks. The best-characterized approach so far to control the activity PCSK9 has been the use of monoclonal antibodies. There have been several clinical trials that tested the use of anti-PCSK antibodies showing high effectivity in the control of serum LDL-C and minimal side effects. This review describes part of those studies and their...
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