fig1

The <i>TNNI3</i> p.R186Q mutation is responsible for hypertrophic cardiomyopathy via promoting FASN-stimulated abnormal fatty acid metabolism

Figure 1. Tnni3R186Q/R186Q mice exhibit cardiomyocyte hypertrophy. (A) The cTnI protein expression level in sections of the ventricles of Tnni3+/+ and Tnni3R186Q/R186Q littermates (n = 3 per group). (B) The survival curve of Tnni3+/+ (n = 91) and Tnni3R186Q/R186Q (n = 78) mice. *P < 0.05, Log-Rank (Mantek-Cox) tests. (C) Representative M-mode echocardiographic images of Tnni3+/+ and Tnni3R186Q/R186Q mice at 10 months old. (D) Gross histological view (longitudinal section) of Tnni3+/+ and Tnni3R186Q/R186Q mice ventricular myocardium stained with HE (pink) and Masson’s trichrome staining (red) to reveal myocardial structure (100×). Scale bar 2 mm. (E) Representative images of WGA staining in Tnni3+/+ and Tnni3R186Q/R186Q mice hearts, showing cardiac myocyte (CM) cross-sectional area. Scale bar 20 µm. (F) Quantitative data of CM hypertrophy assessed by cross-sectional areas;(n = 3 per group with 100 CMs analyzed. ***P < 0.001). (G) HE (pink) and Masson’s trichrome staining (red) of Tnni3+/+ and Tnni3R186Q/R186Q mice ventricular myocardium (cross-section). With HE staining (400×), blue represents the nucleus, and pink represents the cytoplasm. With Masson’s trichrome staining (400×), the collagen fiber is shown blue and cardiomyocytes are red. Scale bar 100 µm. (H) Quantification of total fibrosis for Masson’s trichrome staining of Tnni3+/+ and Tnni3R186Q/R186Q mice ventricular myocardium (cross-section). (I) Western blot analysis of the hypertrophic markers MYH7, ANP and BNP in whole heart tissue of Tnni3+/+ and Tnni3R186Q/R186Q mice (n = 3 per group). The results are expressed as the means ± SEM and a representative experiment is shown. (*P < 0.05, **P < 0.01, ***P < 0.001). The statistical test was done with unpaired T-test. GAPDH was used as the loading control.

The Journal of Cardiovascular Aging

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https://www.portico.org/publishers/oae/