RESUMEN
The lysosome, a key organelle for cellular clearance, is associated with a wide variety of pathological conditions in humans. Lysosome function and its related pathways are particularly important for maintaining the health of the cardiovascular system. In this review, we highlighted studies that have improved our understanding of the connection between lysosome function and cardiovascular diseases with an emphasis on a recent breakthrough that characterized a unique autophagosome-lysosome fusion mechanism employed by cardiomyocytes through a lysosomal membrane protein LAMP-2B. This finding may impact the development of future therapeutic applications.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Susceptibilidad a Enfermedades , Lisosomas/metabolismo , Animales , Autofagosomas/metabolismo , Autofagia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/terapia , Manejo de la Enfermedad , Predisposición Genética a la Enfermedad , Terapia Genética , Enfermedad por Depósito de Glucógeno de Tipo IIb/diagnóstico , Enfermedad por Depósito de Glucógeno de Tipo IIb/etiología , Enfermedad por Depósito de Glucógeno de Tipo IIb/metabolismo , Humanos , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Fusión de Membrana , Proteínas de la Membrana , Mutación , Miocitos Cardíacos/metabolismo , FenotipoRESUMEN
Danon disease (DD) is caused by the absence or malfunction of lysosomal-associated membrane protein 2 (LAMP2). Although Lamp2-deficient mice and DD patients have similar characteristics, these mice have clear limitations and are clinically inconsistent. The aim of our paper is to outline the characteristics of Lamp2-deficient rats and to contrast this model with currently available DD mouse models. The baseline levels of some serum enzymes were elevated in Lamp2y/- rats along with hypercholesterolemia and hyperglycaemia at 8 weeks. Echocardiography showed that IVSd (1.500 ± 0.071 vs. 2.200 ± 1.147, P < 0.01) and LVPWd (1.575 ± 0.063 vs. 1.850 ± 0.029, P < 0.01) were significantly increased, and GCS (-13.20 ± 0.4814 vs. -6.954 ± 0.665) and GRS (21.42 ± 1.807 vs. 7.788 ± 1.140) were sharply decreased. Meanwhile, substantial myocyte disruption, hypertrophic muscle fibres, interstitial fibrosis and microvascular hyperplasia could be observed in the heart tissue. Lamp2y/- rats also displayed abnormal behaviours in the open field and fear conditioning tests. Notably, Lamp2y/- rats manifested other system dysfunctions, such as retinopathy, chronic kidney injury and sterility. Based on these results, Lamp2-deficient rats exhibited greater similarity to DD patients in terms of onset and multisystem lesions than did mouse models, and these rats could be used as a valuable animal model for DD.
