RESUMEN
Hypertrophic cardiomyopathy is a primary disorder characterized by asymmetric thickening of the septum and left ventricular wall, which affects 1 in 500 individuals in the general population. Mutations in mitochondrial DNA have been found to be one of the most important causes of hypertrophic cardiomyopathy. Here we report the clinical, genetic and molecular characterization of a Han Chinese family with a likely maternally transmitted hypertrophic cardiomyopathy. Four (2 men/2 women) of 5 matrilineal relatives in this 3-generation family exhibited the variable severity and age at onset of 44 to 79 years old. Sequence analysis of the entire mitochondrial DNA in this pedigree identified the known homoplasmic ND5 12338T>C variant. This mitochondrial DNA haplogroup belongs to the Eastern Asian F2a. The 12338T>C variant, highly evolutionarily conserved, resulted in the replacement of the translation initiating methionine with a threonine, shortening the ND5 polypeptide by 2 amino acids. The occurrence of ND5 12338T>C variant exclusively in maternal members of this Chinese family suggested that the 12338T>C variant is associated with maternally inherited hypertrophic cardiomyopathy. Our findings will provide theoretical basis for genetic counseling of maternally inherited hypertrophic cardiomyopathy.
Asunto(s)
Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/patología , Complejo I de Transporte de Electrón/genética , Mitocondrias/genética , Proteínas Mitocondriales/genética , Adulto , Edad de Inicio , Anciano , China , ADN Mitocondrial/genética , Ecocardiografía/métodos , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Linaje , Factores de RiesgoRESUMEN
The importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well documented; however, limited information on NK/DC interaction during atherosclerosis is available. Inflammation plays an important role in the development of atherosclerosis, and oxidized low-density lipoprotein (ox-LDL) is believed to play a critical role in the development and progression of atherosclerosis. In this study, we developed a NK/DC coculture system to examine the role of ox-LDL in modulating the interaction of mice NK cells and DCs. Fresh NK cells were cocultured with DCs in the absence or presence of ox-LDL. We examined the cytokines released during the interaction. This report provides the first evidence of an enhancement effect by ox-LDL on the NK/DC crosstalk. Notably, we found that ox-LDL significantly promoted the interaction of NK cells and DCs via CD48-2B4 contact-dependent mechanisms. These findings highlight the importance of NK/DCs crosstalk in atherosclerosis and provide new information about the possible mechanisms of atherosclerosis.