. Circulating microRNA-122 signature in nonalcoholic steatohepatitis and cardiovascular disease: a new endocrine system in metabolic syndrome

SILVIA SOOKOIAN; TOMAS FERNANDEZ GIANOTTI; GUSTAVO O CASTAÑO; CARLOS JOSE PIROLA

HEPATOLOGY (BALTIMORE, MD.)

JOHN WILEY & SONS INC

Lugar: New York; Año: 2013 vol. 57 p. 2545 - 2547

0270-9139

We read with great interest the article by Bala S. et al. about the role of circulating microRNAs (miRNAs) as markers of alcohol and acetaminophen induced- liver damage in a mice model; the authors concluded that circulating miR-122 and miR-155 may serve as biomarkers of liver injury and inflammation, respectively 1. The concept that miRNAs in serum/plasma are powerful potential biomarkers for liver diseases has expanded very quickly in the last years, and the role of circulating miR-122 in predicting liver damage has been replicated in liver diseases of different etiologies, including human nonalcoholic fatty liver disease (NAFLD) 2. In fact, we evaluated the circulating expression of a panel of 84 miRNAs in serum of patients with NAFLD proven through biopsy in a case-control design, and we observed that miR-122 was significantly up-regulated in NAFLD patients compared to control subjects, and the fold increase was strongly related to the disease severity (NASH versus simple steatosis: 3.14 and versus control subjects: 7.2, fold change). Thus, we agree that circulating miR-122 is a robust biomarker for predicting NAFLD progression, and perhaps is able to solve the dilemma of how useful are aminotransferases to decide patients?f monitoring and liver biopsy indication because its performance seems to be much better 1, 2.    Certainly, the role of circulating miRNAs in clinical scenarios is not restricted to disease monitoring; miRNAs circulate in the bloodstream and are taken up by distant cells, therefore, they have the enormous potential of regulating the expression of more than 170 highly interacting genes (figure) simultaneously in different tissues/cells being a truly new endocrine system. In this scenario, we provide some preliminary evidence about circulating miR-122 could be also regarded as a powerful biomarker for cardiovascular disease in patients with NAFLD. For instance, we explored in a case control study of 300 individuals with NAFLD, a gene variant (rs41318021) in the 3??-UTR of human l-arginine transporter SLC7A1, which was associated with genetic predisposition to essential hypertension. The 3??-UTR of human SLC7A1 contains a predicted miR-122 binding site that may play a role in controlling gene expression 3. Interestingly, we found that in patients with NAFLD the rs41318021 was significantly associated with arterial systolic/diastolic hypertension (OR 2.057, CI 95% 1.279-3.294, p