DOI: 10.1161/circ.148.suppl_1.15581 ISSN: 0009-7322

Abstract 15581: Increasing Myocardial Carnosine Levels Reduces Adverse Remodeling During Heart Failure

Benjamin Doelling, David Hoetker, Kenneth Brittian, Robert E Brainard, Aruni Bhatnagar, Shahid P Baba
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Background : Lipid peroxidation products, such as acrolein, are highly toxic aldehydes generated during pathological remodeling and associated with heart failure. Until now, no translatable therapy has been tested to remove these toxic products from heart and examine the subsequent effects on failing hearts. The heart contains small histidyl dipeptides, such as carnosine (β-alanine-histidine), which bind lipid peroxidation products. Carnosine is decreased in failing hearts and its levels can be increased by supplementing the precursor, β-alanine. This study investigates the cardioprotective and translational potential of β-alanine supplementation in a transaortic constriction (TAC) model of heart failure.

Hypothesis : Increasing myocardial carnosine via β-alanine supplementation will improve cardiac function during heart failure.

Approach : Male wild-type C57BL/6J mice were treated either (a) water alone, (b) β-alanine 1 week prior to TAC, or (c) β-alanine (20g/L) in water 4 weeks post TAC. Supplementation of β-alanine was continued for 8 weeks, followed by serial echocardiography, biochemical, and mass spectrometry analysis.

Results : Myocardial carnosine increased ~3-4-fold after 1 week of β-alanine feeding compared with water alone (p < 0.05). β-alanine pre-feeding compared with water alone, after 8 weeks of TAC, decreased left ventricular (LV) mass (β-alanine: 174 ± 29 vs water: 241 ± 17 mg, p < 0.05) and LV inner diameter at systole (β-alanine: 2.2 ± 0.6 vs water: 3.5 ± 0.4 mm, p < 0.05) and diastole (β-alanine: 3.5 ± 0.4 vs water: 4.4 ± 0.3 mm, p < 0.05), and increased ejection fraction (β-alanine: 67 ± 14% vs water: 42 ± 9%, p < 0.05) and cardiac output (β-alanine:13.6 ± 2.6 vs water: 10.7 ± 1.0 mL/min, p < 0.05). Post-TAC β-alanine intervention decreased LV mass (β-alanine :177 ± 8 vs water: 214 ± 11 mg, p < 0.05), hypertrophic markers Nppa and Myh7 , and increasingly removed acrolein from heart by conjugation (β-alanine: carnosine-propanal: 12.2 ± 0.4 vs water: 0.7 ± 0.4 pmoles/mg protein, p < 0.0001).

Conclusion : Increasing myocardial carnosine via oral supplementation alleviates pathological remodeling, possibly through quenching reactive aldehydes. These findings lay foundation to test the feasibility of β-alanine in heart failure patients.

More from our Archive