A deficiency in the gene for endonuclease G (Endog) was recently described as a genetic determinant of cardiac hypertrophy. The mechanisms involved in the regulation of Endog, however, are still to be elucidated. Therefore we hypothesised that Endog, being regulated by small regulatory non-coding RNAs called microRNAs (miRNAs), could contribute to the cardiac hypertrophy of the Hypertrophic Heart Rat (HHR), a human polygenic model of cardiac hypertrophy. From birth the HHR has less and smaller cardiomyocytes, which leads to hypertrophy and cardiac failure later in life. In this study, we examined genome-wide miRNA expression by Agilent Rat miRNA Microarray Kit Release 16.0 and Endog mRNA levels by real-time PCR in the left ventricle of neonatal HHR compared to age-matched rats from its authentic control, the Normal Heart Rat (NHR). Endog mRNA was significantly under-expressed in the HHR (fold change=−4.7; P=0.0001). Sixty-seven miRNAs (FDR P<0.05 and fold change>1.1) were differentially expressed between HHR and NHR (n=16). We then performed an in silico analysis to predict the miRNAs that are able to bind to the 3′ untranslated region of Endog mRNA, and therefore could regulate Endog levels. We discovered that the miRNAs let-7b, miR-338 and miR-347 are predicted to bind to Endog mRNA. Functional studies are being undertaken to determine whether these miRNAs can regulate Endog mRNA levels in vitro and their role in the pathological processes leading to cardiac hypertrophy. These miRNAs could be a new target for the prevention and treatment of cardiac hypertrophy in humans
Type 2 diabetes (T2D) is a chronic metabolic disorder that is predominately associated with lifestyle changes including reduced physical activity, poor nutrition and obesity. Despite major medical advances in the treatment of T2D, its prevalence is still increasing at an alarming rate. Accordingly, better management and prevention strategies are urgently needed to prevent the development and progression of this disease. In the last decade there have been considerable efforts to improve public health through alternative research paradigms. Community-Based Participatory Research (CBPR) is one such process by which researchers form an equal and transparent partnership with the community with the final goal of creating empowerment and societal change to facilitate action and provide solutions to promote health and well-being. One CBPR program, the Kahnawake Schools Diabetes Prevention Project (KSDPP), was initiated to promote increased physical activity and healthier eating habits among school children based on the Mohawk’s “Living in Balance” philosophy. Utilizing CBPR principles, KSDPP engaged researchers and the community in all stages of the research processes. This project was community driven from the beginning and was independent of any external institutional change agent to facilitate community action and the implementation of strategies to find solutions. Although the project has been instrumental in community empowerment and societal change, several challenges remain. Accordingly, understanding the unique social, environmental and historical context that shapes lifestyle and risk factors for T2D in Native populations will help to understand the unique nature of this disease in these groups.