Aging and Chronic Acetaminophen Administration Effects on MicroRNA Expression in Fischer 344/NNia X Brown Norway/BiNia Rat Hearts

Abstract

PURPOSE: Cardiovascular disease (CVD) is responsible for more than 30% of all deaths worldwide and heart failure is the leading cause of death in individuals over age 65. Although not well understood it is thought that the profound impact of age on the risk of the occurrence, severity and prognosis of cardiovascular disease is due, in part, to age-associated changes in cardiovascular structure and/or function. Recent research has shown that microRNAs including miR-23a, miR-23b, and miR-24 may play a role in the progression of structural and functional deficit. The effect of aging and chronic acetaminophen treatment was examined in Fischer 344 X Brown Norway (FBN) rats. METHODS: Aging male FBN rats (27 month-old; n=8) were treated with therapeutic doses of acetaminophen (30mg/kg/day p.o.) for 6 months. Age-matched control rats (n=8) did not receive any drug treatment. Hearts from untreated 6-month-old rats were used as young controls. The expression of microRNAs in hearts from these groups was compared by quantitative RT-PCR. RESULTS: The expression of miR-23a, miR-23b, and miR-24 in 33mo hearts was found to be 0.48 ± 0.20, 0.20 ± 0.04, 0.12 ± 0.04 times that of 6mo controls, respectively (p < 0.05). Expression of miR-23b in 33mo acetaminophen treated hearts was 20.51 ± 5.64 times that of the untreated 33mo controls, while the expression of miR-24 was 0.032 ± 0.02 times. CONCLUSIONS: These results indicate that expression of miR-23a, miR-23b, and miR-24 is altered in the aging heart in addition to affected by acetaminophen treatment. Further investigation of these microRNAs will help in pharmacological treatment of cardiovascular disease.