Javier Beaumont, Begoña López, Susana Ravassa, Javier Díez, Arantxa González et al.
Description of the technology
The study, carried out to support this technology, 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 collagen fibril cross-linking. This research was performed 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 microRNA-19b (miR-19b) presented a direct correlation (p < 0.05) between its serum level and myocardial level. 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 level of miR-19b were inversely correlated (p < 0.05) with LOX, collagen fibril cross-linking and left ventricular (LV) chamber stiffness in AS patients. In process of in vitro studies miR-19b inhibition increased (p < 0.05) connective tissue growth factor protein and LOX protein expression in human fibroblasts.
Conclusion was made that decreased content of miR-19b may be involved in myocardial LOX up-regulation and excessive collagen fibril cross-linking, and consequently increased left ventricular chamber stiffness in AS patients, particularly, in those with HF. Serum miR-19b can be a biomarker of these alterations of the myocardial collagen network in AS patients, especially, in patients with HF.
This technology can be applicable in clinical and experimental cardiology for diagnostics of a number of heart diseases on the basis of myocard condition (by measurement of serumal and miocardial levels of miR-19b), because circulating miR-19b emerges as a potential biomarker of the alterations of myocardial collagen present in aortic stenosis patients with heart failure.
Besides, since miR-19b has been shown to regulate connective tissue growth factor in ageing-associated heart failure both in rodents in experiments and in human patients, this technology can be used with the aim of development of heart failure experimental models for the investigations in the field of cardiology and ageing mechanism study.
- Program of Cardiovascular Diseases, Centre for Applied Medical Research, University of Navarra, Pamplona (Spain)
- IdiSNA, Navarra Institute for Health Research, , Pamplona (Spain)
- Institute of Experimental and Clinical Research, University of Louvain (UCL) Medical School, Brussels (Belgium)
- Department of Cardiology and Cardiovascular Surgery, University of Navarra Clinic, , Pamplona (Spain)
- Beaumont, J. et al. «MicroRNA-19b is a potential biomarker of increased myocardial collagen cross-linking in patients with aortic stenosis and heart failure." 7 Scientific Reports (2017): 40696.
- López, B. et al. «Myocardial collagen cross-linking is associated with heart failure hospitalization in patients with hypertensive heart failure." 67 J Am Coll Cardiol. (2016): 251–260.
- Beaumont, J. et al. «MicroRNA-122 down-regulation may play a role in severe myocardial fibrosis in human aortic stenosis through TGF-beta1 up-regulation." 126 Clin Sci. (2014): 497–506.