Role of tripartite motif-containing protein 59 in pathological cardiac hypertrophy

YANG Ning; WANG Chao; LIU Yan-yi; HUANG Zhen-yu; SHI Xin; DING Fang-bao; MEI Ju; JIANG Zhao-lei

doi:10.3969/j.issn.1672-5301.2025.12.014

Abstract：Objective This study aimed to evaluate the expression and function of tripartite motif-containing protein 59(TRIM59)in cardiac hypertrophy through animal and cardiomyocyte models,and to elucidate its underlying molecular mechanisms in pathological hypertrophy,thereby providing a potential therapeutic target for intervention.Methods From March to May 2025,a pressure-overload cardiac hypertrophy model was generated in mice via transverse aortic constriction(TAC)in the laboratory of Xinhua Hospital,Shanghai Jiao Tong University School of Medicine.Twenty-four mice were assigned to four groups(n=6 each):the Sham group,TAC-2W group,TAC-4W group and TAC-6W group,and a sham-operated group served as the control.The cardiac function was evaluated by transthoracic echocardiography,including ejection fraction(EF),fractional shortening(FS),left ventricular internal diameter in diastole(LVIDd)and left ventricular posterior wall diastole(LVPWd).The cardiac hypertrophy and myocardial fibrosis were assessed by hematoxylin-eosin(HE),Masson's trichrome and Sirius Red.RT-qPCR and Western blotting were employed to analyze the transcriptional and translational levels of hypertrophic markers(ANP,BNP and MYH7)and fibrotic markers(COL1A1,CTGF).In vitro,the neonatal rat cardiomyocytes(NRCM)and human cardiomyocyte cells(AC16)were transfected with small interfering RNA to suppress TRIM59 expression,thereby evaluating its regulatory role in hypertrophy,fibrosis,oxidative stress and apoptosis.All experiments were independently repeated at least three times,and statistical analyses were performed to ensure data robustness.Results The TRIM59 expression was markedly upregulated in TAC-induced pathological cardiac hypertrophy in mice,concomitantly with the elevation of hypertrophic and fibrotic markers.In the NRCM and AC16 cells,TRIM59 knockdown further augmented the expression of hypertrophy-and fibrosis-related genes and exacerbated oxidative stress and apoptosis.Moreover,the myocardial tissues from patients with hypertrophic cardiomyopathy also demonstrated significantly increased expression of TRIM59 and related molecules.Conclusion TRIM59 plays a critical protective role in pressure overload-induced pathological cardiac remodeling,and its upregulation may represent a compensatory regulatory response to myocardial injury.In contrast,the loss of TRIM59 markedly exacerbates cardiac hypertrophy,fibrosis and cellular damage,thereby disrupting myocardial homeostasis.TRIM59 may serve as a potential therapeutic target for the intervention of cardiac hypertrophy and heart failure.