title: KLK1 and ZG16B proteins and arginine-proline metabolism identified as novel targets to monitor atherosclerosis, acute coronary syndrome and recovery.
abstract: We pursued here the identification of specific signatures of proteins and metabolites in urine which respond to atherosclerosis development, acute event and/or recovery. An animal model (rabbit) of atherosclerosis was developed and molecules responding to atherosclerosis silent development were identified. Those molecules were investigated in human urine from patients suffering an acute coronary syndrome (ACS), at onset and discharge. Kallikrein1 (KLK1) and zymogen granule protein16B (ZG16B) proteins, and l-alanine, l-arabitol, scyllo-inositol, 2-hydroxyphenilacetic acid, 3-hydroxybutyric acid andN-acetylneuraminic acid metabolites were found altered in response to atherosclerosis progression and the acute event, composing a molecular panel related to cardiovascular risk. KLK1 and ZG16B together with 3-hydroxybutyric acid, putrescine and 1-methylhydantoin responded at onset but also showed normalized levels at discharge, constituting a molecular panel to monitor recovery. The observed decreased of KLK1 is in alignment with the protective mechanism of the kallikrein-kinin system. The connection between KLK1 and ZG16B shown by pathway analysis explains reduced levels of toll-like receptor 2 described in atherosclerosis. Metabolomic analysis revealed arginine and proline metabolism, glutathione metabolism and degradation of ketone bodies as the three main pathways altered. In conclusion, two novel urinary panels of proteins and metabolites are here for the first time shown related to atherosclerosis, ACS and patient's recovery.
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martin-Lorenzo
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Zubiri
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Aroa S
authors.initials: AS
authors.lastname: Maroto
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Gonzalez-Calero
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Posada-Ayala
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cuesta
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mourino-Alvarez
authors.affiliation: Department of Cardiac Surgery, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Lopez-Almodovar
authors.affiliation: Ibermutuamur, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Calvo-Bonacho
authors.affiliation: Cardiovascular Risk and Hypertension, Instituto de Investigacion Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruilope
authors.affiliation: Department of Cardiology, Hospital Virgen de la Salud, SESCAM, Toledo, Spain.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Padial
authors.affiliation: Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Barderas
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain ; Department of Biochemistry and Molecular Biology I, UCM, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Vivanco
authors.affiliation: Department of Immunology, IIS-Fundacion Jimenez Diaz, UAM, REDinREN, Avenida Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Alvarez-Llamas
keywords: Acute coronary syndrome; Kallikrein; MRM; Metabolites; Nuclear magnetic resonance; SRM; Urine; Zymogen granule protein