RESUMEN
BACKGOUND: The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets. METHODS: Here we describe the human arterial proteome and proteomic features strongly associated with early atherosclerosis based on mass spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling, and bioinformatic analyses defined the composition, network rewiring, and likely regulatory features of the protein networks associated with early atherosclerosis and how they vary across 2 anatomic distributions. RESULTS: The data document significant differences in mitochondrial protein abundance between coronary and aortic samples (coronary>>aortic), and between atherosclerotic and normal tissues (atherosclerotic<Asunto(s)
Aorta/química
, Enfermedades de la Aorta/metabolismo
, Aterosclerosis/metabolismo
, Enfermedad de la Arteria Coronaria/metabolismo
, Vasos Coronarios/química
, Proteínas/análisis
, Proteómica/métodos
, Espectrometría de Masas en Tándem
, Adolescente
, Adulto
, Aorta/patología
, Enfermedades de la Aorta/patología
, Aterosclerosis/patología
, Autopsia
, Biomarcadores/análisis
, Enfermedad de la Arteria Coronaria/patología
, Vasos Coronarios/patología
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Placa Aterosclerótica
, Mapas de Interacción de Proteínas
, Adulto Joven
RESUMEN
Cathepsins are proteolytic enzymes typically located within the lysosomes of macrophages. Once released, they can enhance the inflammatory process in atherosclerosis. Cathepsin X aids in the migration of T-lymphocytes and the release of cytokines. Cathepsin D modifies low-density lipoprotein to promote its uptake by macrophages and its subsequent foam cell formation. Furthermore, cathepsin D regulates apoptosis. Cathepsin B degrades the extracellular matrix within the arterial intima. Together, they increase plaque vulnerability. This evidence suggests that cathepsins play an important role in the pathogenesis of atherosclerosis.