The FVB mouse strain as a spontaneous model of degenerative mitral valve disease

Mitral valve disease is a complex entity with diverse origins, degeneration occurring following an extrinsic aggression (infection, autoimmune attack, drug), genetic malformation or being due to a hemodynamic abnormality (dilatation of the left ventricle, myocardial infarction). The aim is to present the main cardiovascular characteristics of the FVB mouse strain with a particular focus on spontaneous mitral valve degeneration and the serotonergic system in comparison with the C57BL/6 J, the usual background strain of many cardiovascular studies. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-β1 and plasma natriuretic peptide concentrations were measured in FVB/NJ and FVB/NRj mice strains (males and females) obtained from Janvier and Charles River Labs in comparison to the usual C57BL/6 background at different ages (12, 16, 20 and 24-week-old). To know if the mitral valve was remodeled, cardiac anatomy and function were assessed by echocardiography and mitral valves were finally characterized by histology. The expression of 5-HT2A and 5-HT2B receptors was measured by RTqPCR in the anterior leaflet of the valve. No significant difference in C57BL/6 J compared to FVB mice strains regarding body weight increase, arterial blood pressure and heart rate was observed. A progressive augmentation of plasma pro-ANP was observed in FVB mice. However, no cardiac hypertrophy or left-ventricular fibrosis were observed. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length (100% of 24-week-old FVB/NRj males). The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. No difference regarding serotonergic receptors expression was observed. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium meaning the absence of mitral valve prolapse. Spontaneous mitral myxomatous degeneration is highly prevalent in FVB mice. A contribution of the serotonergic system is suggested