Abstract
Ageing is a well-established risk factor for cardiovascular diseases (CVDs). One of the critical risk factors of age-associated CVDs is dysregulation in the expression of microRNAs (miRNA). However, the fundamental mechanisms, including the specific age at which dysregulation occurs and whether this dysregulation is similar in both sexes, remain unclear. Therefore, we aimed to determine the age-associated changes in the expression of cardiac-specific/enriched miRNAs such as miR-1, -9, -34a, -126, -133, -208 (target miRNAs) and their effect on the cardiovascular system.
The expression levels of target miRNAs were quantified in the cardiac tissue of Drosophila melanogaster (n=5) and C57BL/6 mouse (n=5). Cardiac tissue from male and female Drosophila were collected at 7-day intervals up to 70 days. Cardiac tissue from male and female C57BL/6 mice were collected every 6 weeks from 18 to 72 weeks of age. The expression of target miRNAs were analyzed using reverse transcription-polymerase chain reaction (RT-PCR).
Preliminary results from male Drosophila indicate a significant downregulation of miR-9 (P = 0.0002), miR-133 (P < 0.0001) with age, consistent with an increased risk of cardiac hypertrophy and fibrosis, respectively. In female mouse hearts, the expression of miR-1 (P = 0.0007), miR-9 (P= <0.0001) were significantly downregulated whereas miR-126 (P= 0.01), miR-133 (P = 0.009), miR-208 (P < 0.0001) were upregulated with age. Dysregulated expression of miR-1, -9, -208, and -133 indicate an increased risk of arrhythmia (miR-1), cardiac hypertrophy (miR-9, -208), and fibrosis (miR-133) with age.
Preliminary results indicate aging is associated with significant dysregulation of cardiac-specific miRNAs, implicating a heightened risk of age-related cardiovascular conditions such as arrhythmia, cardiac hypertrophy, and fibrosis.