The heart requires large amount of energy to supportits constant contractions and other physiological activities.
Due to the highenergy demand of the heart to function, cardiomyocytes have high mitochondrialdensity with it taking up over 35% of total cell volume as compared to othertissues besides their ability to metabolize a wide range of energy substratesincluding carbohydrates, lipids, amino acids and ketone bodies to meet theirenergy requirements1,2. It is well establishedthat the energy metabolism of cardiomyocytes are tightly regulated and changesas they mature; where initially the fetal cardiomyocytes are highly dependenton glycolysis for energy which later on switch to fatty acid b-oxidation when they mature andbecome differentiated as seen in adultcardiomyocytes3. Interestingly, the metabolism of mature cardiomyocytes willswitch back to glycolysis as their energy source if hypertrophic stressdevelops4-6.
By monitoring the expression of genes involved in thesemetabolic pathways of glycolysis and b-oxidation could be used to study the changes and identify thematuration/disease stage in which the cardiomyocyte is in. In humans, the accumulation of oxidative stressresults in cardiac hypertrophy and diseased cardiomyocytes. Hypertrophy causesthe cardiomyocytes to revert to the glycolysis-dependent fetal-like form,weakening the contraction of the heart. This also occurs during the naturalprocess of ageing. Antioxidants, including Vitamin C, have been proven to slowdown the progression of ageing by neutralising free radicals responsible forthis7. Henceforth, in this proposal, weaim to investigate the beneficial effects of tocotrienol compounds(anti-oxidants) in promoting cardiomyocyte maturation and/or protection againstcardiac hypertrophy using a human glycolysis metabolic reporter cell line.
This metabolic reporter system will reflect changes inmetabolic pathways (glycolysis vs b-oxidation), therebyallowing us to track the cellular status of cardiomyocytes (fetal-like, matureor undergoing cardiac hypertrophy) by quantitating the usage of differentmetabolic pathways based on colorimetric analysis.