Cardiac myosin-binding protein C (cMyBP-C) gene mutations are associated with familial hypertrophic cardiomyopathy. Heterozygous cMyBP-C null mice (Het) develop left ventricular hypertrophy (LVH) at 10-11 months old. Previous studies showed that a high salt dietinduces LVH in normal mice. Therefore, this study examined whether a genetic predisposition to LVH infl uences both the LVH response to a high salt diet and the expression level of the sarcomeric genes and the molecular maker of LVH.
Het and age-matched wide type (WT) mice (5 months old) were subjected to a regular salt diet (RS, 0.6 % NaCl) or to a high salt diet (HS, 4 % NaCl) for 8 weeks. LVH response was achieved by the measurements of the heart morphometric parameters. Gene expression level was quantified by absolute RT-qPCR.
Arterial pressure was similar in all groups at baseline and after 8 weeks of diet (from 122±2 to 126±6 mmHg). After 8 weeks of HS diet, the heart weight (HW) to body weight (BW) ratio of Het and WT mice was increased by 23 % and 17.5 % respectively compared to RS diet. In Het mice the HW/BW ratio was higher in both RS (+10 %) and HS (+5 %) diets than in controls. The increase of the HW/BW ratio was related to the increase of the LV weight in both groups (+25 % in Het and +22 % in WT). The expression levels of the sarcomere genes MYBPC3, ACTC1, MYH6, TTN were similar in all groups in both diets. FHL1 and NPPB expression levels were higher in Het than in WT mice but remained stable in both diet conditions. In conclusion, in Het mice, HS majors LVH without modification of both the arterial pressure and the expression levels of the major sarcomere genes. FHL1 and NPPB expression levels were increased only in Het mice without infl uence of the HS diet. This suggests that FHL1 and NPPB are involved in the LVH response due to the genetic predisposition, independently of the activation of hypertrophic signalling pathways induced by the HS diet.Le texte complet de cet article est disponible en PDF.