Status: Funded - Closed
A circulating miRNA phenotype of early myocardial remodeling in adolescent obesity
Ravi Shah, M.D.
BACKGROUND: Over the last 30 years, adolescent obesity has more than tripled, with nearly 20% of children between 2-19 classified as obese. The cardiovascular phenotype of adult obesity originates in adolescence, suggesting the adolescent life-stage as a promising locus to improve future cardiovascular health. The first step to address cardiovascular risk in the young is to identify obese adolescents at highest risk for adverse outcomes.
GAP: Potential endocrine effects of circulating miRNAs on myocardial biology (a “cross-talk” between obesity/inflammation and the heart) provide a tantalizing new paradigm for early myocardial remodeling in adolescence—a “primordial” HF phenotype for early prevention/intervention. Establishing a miRNA profile of obesity-related cardiac remodeling would be an important step toward defining a role for circulating miRNAs as biomarkers of early cardiac disease in adolescents.
HYPOTHESIS: We hypothesize that altered myocardial tissue structure (defined by left ventricular mass and global and regional myocardial systolic and diastolic function by echocardiography) in adolescent obesity are associated with circulating microRNAs common to pediatric obesity and adult heart failure.
METHODS: We plan to enroll obese and lean adolescents and perform comprehensive 2D-/3D-echocardiography. We will assay selected RNAs and biochemical markers of obesity and cardiac remodeling.
RESULTS: Currently, we have established a circulating RNA phenotype of cardiometabolic diseases, with publically available data from the Framingham Heart Study and a cohort of 90 obese/overweight adolescents from the Boston Children’s Hospital.
IMPACT: Collectively, the co-existence of a common miRNA profile between pediatric obesity and adult HF suggests that circulating miRNAs elevated in pediatric obesity may illuminate molecular pathways important to early myocardial remodeling. Examining associations between early myocardial changes by CMR and candidate plasma extracellular miRNAs in pediatric obesity bridges a critical gap: it will implicate miRNAs as novel “cardio-endocrine” biomarkers for early disease (and potentially even as targets for intervention) to prevent the future diabetes and obesity-related cardiac complications.