miRNAs in Uremic Cardiomyopathy: A Comprehensive Review

Abstract

Uremic Cardiomyopathy (UCM) is an irreversible cardiovascular complication that is highly pervasive among chronic kidney disease (CKD) patients, particularly in End-Stage Kidney Disease (ESKD) individuals undergoing chronic dialysis. Features of UCM are an abnormal myocardial fibrosis, an asymmetric ventricular hypertrophy with subsequent diastolic dysfunction and a complex and multifactorial pathogenesis where underlying biological mechanisms remain partly undefined. In this paper, we reviewed the key evidence available on the biological and clinical significance of micro-RNAs (miRNAs) in UCM. miRNAs are short, noncoding RNA molecules with regulatory functions that play a pivotal role in myriad basic cellular processes, such as cell growth and differentiation. Deranged miRNAs expression has already been observed in various diseases, and their capacity to modulate cardiac remodeling and fibrosis under either physiological or pathological conditions is well acknowledged. In the context of UCM, robust experimental evidence confirms a close involvement of some miRNAs in the key pathways that are known to trigger or worsen ventricular hypertrophy or fibrosis. Moreover, very preliminary findings may set the stage for therapeutic interventions targeting specific miRNAs for ameliorating heart damage. Finally, scant but promising clinical evidence may suggest a potential future application of circulating miRNAs as diagnostic or prognostic biomarkers for improving risk stratification in UCM as well.

Chronic kidney disease associated cardiomyopathy: recent advances and future perspectives

“…Recent reports in dialysis [74] and transplant [75] patients show a correlation between the cardiotonic steroid, marinobufagenin and echocardiographic findings that reflect uremic cardiomyopathy. Several miRNAs have also been implicated in the pathophysiology of CKD-associated cardiomyopathy [76][77][78]. Table 1 presents a summary of recently studied biomarkers in the context of CKDassociated cardiomyopathy.…”

New Insights on the Role of Marinobufagenin from Bench to Bedside in Cardiovascular and Kidney Diseases

“…Although extracellular volume expansion is thought to be crucial for the development of UC, there is still much debate about the exact pathogenesis [ 94 , 95 , 96 ]. Immunization against MBG in partial nephrectomy animals was associated with a substantial attenuation of cardiac hypertrophy, cardiac fibrosis and the oxidant stress state [ 97 ].…”

Advances in the study of miRNAs in chronic kidney disease with cardiovascular complications

“…This might potentially elucidate the reason for the disruption of gonadotropin signalling and the deterioration of chronic kidney disease (CKD) when miR-146b-5p is inhibited. Further investigation is required to explore the potential involvement of additional miRNA families in regulating hormonal responses to cardiac pathology during chronic kidney disease (CKD) (D'Agostino et al, 2023). The aforementioned studies not only provide insights into a hitherto unidentified mechanism of left ventricular hypertrophy (LVH) production in chronic kidney disease (CKD) but also propose prospective therapeutic targets for managing cardiac hypertrophy in CKD patients (refer to Table 2).…”