P247Molecular alterations in human urine reveal atherosclerosis development, cardiovascular event at onset and follow-up

Purpose: Search of progression and recovery markers in atherosclerosis disease. Methods: An animal model of early atherosclerosis was done in rabbits fed with different diets, regular diet and cholesterol-rich (control and pathological group). Urine samples from animals were analyzed in the search for alterations of the proteome and metabolome (by 2DE-DIGE and NMR, respectively). Confirmation analyses were performed by SRM-(LC-MS/MS). In a pilot translational study, human urine samples from healthy donors and NSTEACS patients at the onset and discharge were analyzed. Results: Four proteins were found significant altered between the two animal groups. Cathepsin D is increased in urine from pathological animals and Hemopexin, Kallikrein 1 (KLK1) and Zymogen granule protein 16B (ZG16B) are decreased. After translational studies KLK1 and ZG16B are proposed to be markers of both, progression and recovery. NMR pops up twenty metabolites significantly varied at early stages of atherosclerosis between animal groups. Eight metabolites increased in urine from pathological animals and twelve metabolites showed the opposite trend (decreased). Two panels of six and three metabolites are found as responders to atherosclerosis progression or recovery from an acute event, respectively. Metabolism changes of particular sugars, hydroxy acids, amino acids, cyclic alcohols, polyamines and imidazolidines are here shown to be associated to atherosclerosis. Conclusions: These data confirm that omics approaches are extremely valuable for the diagnosis and monitoring of atherosclerotic pathologies. Four proteins and twenty metabolites are significantly altered in an early animal model of atherosclerosis. In human samples, two novel urinary panels of proteins and metabolites are here first shown able to monitor atherosclerosis progression and recovery from an acute event.