title: MicroRNA-19b is a potential biomarker of increased myocardial collagen cross-linking in patients with aortic stenosis and heart failure.
abstract: This study analyzed the potential associations of 7 myocardial fibrosis-related microRNAs with the quality of the collagen network (e.g., the degree of collagen fibril cross-linking or CCL) and the enzyme lysyl oxidase (LOX) responsible for CCL in 28 patients with severe aortic stenosis (AS) of whom 46% had a diagnosis of chronic heart failure (HF). MicroRNA expression was analyzed in myocardial and blood samples. From the studied microRNAs only miR-19b presented a direct correlation (p < 0.05) between serum and myocardium. Compared to controls both myocardial and serum miR-19b were reduced (p < 0.01) in AS patients. In addition, miR-19b was reduced in the myocardium (p < 0.01) and serum (p < 0.05) of patients with HF compared to patients without HF. Myocardial and serum miR-19b were inversely correlated (p < 0.05) with LOX, CCL and LV stiffness in AS patients. In in vitro studies miR-19b inhibition increased (p < 0.05) connective tissue growth factor protein and LOX protein expression in human fibroblasts. In conclusion, decreased miR-19b may be involved in myocardial LOX up-regulation and excessive CCL, and consequently increased LV stiffness in AS patients, namely in those with HF. Serum miR-19b can be a biomarker of these alterations of the myocardial collagen network in AS patients, particularly in patients with HF.
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Beaumont
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: López
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Ravassa
authors.affiliation: Institute of Experimental and Clinical Research, University of Louvain (UCL) Medical School, B-1200 Brussels, Belgium.
authors.forename: Nerea
authors.initials: N
authors.lastname: Hermida
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
authors.forename: Gorka
authors.initials: G
authors.lastname: San José
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
authors.forename: Idoia
authors.initials: I
authors.lastname: Gallego
authors.affiliation: Division of Cardiology, Virgen de la Victoria University Hospital, 29010 Málaga, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Valencia
authors.affiliation: Division of Cardiology, Virgen de la Victoria University Hospital, 29010 Málaga, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Gómez-Doblas
authors.affiliation: Division of Cardiology, Virgen de la Victoria University Hospital, 29010 Málaga, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: de Teresa
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.|Department of Cardiology and Cardiovascular Surgery, University of Navarra Clinic, 31008 Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Díez
authors.affiliation: Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, 31008 Pamplona, Spain.|IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: González
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers; D003094:Collagen / Q000378:metabolism*; D015897:Comorbidity; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D034622:RNA Interference; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D003094:Collagen