Producción CyT
Physiological Minireviews - PATHOPHYSIOLOGICAL ROLE OF INOSITOL 1, 4, 5-TRIPHOSPHATE RECEPTOR (IP3R) BINDING PROTEIN RELEASED WITH IP3 (IRBIT) IN THE MYOCARDIUM.
Congreso
Autoría:
Di Mattia RA ; Gallo D ; Ciarrocchi S ; Gonano LA ; Blanco PG ; Portiansky E ; Valverde CA ; Ciancio MC ; Bleckwedel F ; Zelarayan LC ; AIELLO, ERNESTO ALEJANDRO ; Orlowski AFecha:
2023Editorial y Lugar de Edición:
SAFISResumen *
Introduction: IP3R binding protein released with IP3 (IRBIT) was originally identified as a competitive inhibitor of the receptor. Cardiac hypertrophy has been associated with increased generation of IP3 and overexpression of IP3R was found in both human and animal models of heart failure. Given the involvement of IP3R in cardiac hypertrophy, it is plausible that IRBIT may also play a role in this pathological process. Aims: Although IRBIT heart expression has been reported, its function in cardiac tissue remains unclear. Thus, we aimed to study the cardiac outcomes of up and down-regulating IRBIT to establish its pathophysiological role. Materials and methods: We conducted IRBIT overexpression experiments in neonatal and 3-month-old male mice using AAV9-IRBIT-mCherry (5x1011 and 3x1011 vp, respectively), with AAV9-mCherry/saline as controls. For IRBIT downregulation, 3-month-old male mice received AAV9-shIRBIT (4x10^11 vp) or saline. Echocardiography analysis was performed. Cardiac hypertrophy and fibrosis-related molecular markers were measured. IRBIT expression was evaluated in human cardiomyopathy heart samples. Shapiro-Wilk normality test and Student´s t-test or two-way ANOVA were used. Results: IRBIT overexpressed mice showed an increase in left ventricular mass index (LVMI: Saline: 3.55±0.23, n=11; AAV9-IRBIT*: 5.61±0.7, n=8; p<0.05 vs. Saline) and a decrease in cardiac systolic function. Moreover, an augmented heart weight to body weight ratio was found. Cardiac hypertrophy markers (Nppa, MYH7) were significantly increased in IRBIT-upregulated mice. Conversely, IRBIT downregulation did not alter cardiac hypertrophy parameters and fibrosis molecular markers. We evaluated IRBIT expression in human dilated and ischemic cardiomyopathy hearts samples and we discovered IRBIT was differentially expressed: it was reduced in dilated cardiomyopathy patients and increased in ischemic cardiomyopathy patients. Conclusion: Data presented here support IRBIT as a novel cardiac protein involved in cardiac hypertrophy development. Further research is needed to fully elucidate the precise mechanisms through which IRBIT influences heart function, as well as its potential as a therapeutic target in cardiovascular diseases. Información suministrada por el agente en SIGEVAPalabras Clave
IRBITHeartNBCIP3