Abstract 9225: The Role of Leucine/Alpha-KIC/HMB Metabolism Pathway in Vascular Aging

Introduction: Vascular aging, starting from youth, encompasses arterial degeneration and hardening that impairs vascular function, and ultimately causes end-organ damage, predominantly in the heart, brain, and kidney. Leucine (Leu) is an essential amino acid in the biosynthesis of proteins. It is initially catalyzed to α-ketoisocaproate (α-KIC), and then further metabolized to β-hydroxy-β-methylbutyrate (HMB). Our prior work showed a significant decrease in circulating HMB in response to additional sodium intake, a key risk factor for accelerated vascular aging. Hypothesis: We aimed to test the hypotheses that Leu/α-KIC/HMB metabolic activity declines with chronological aging, and that Leu/α-KIC/HMB metabolism is inversely associated with vascular aging in a young population. Methods: Global metabolomic profiling was performed in blood samples from 65 black adolescents and young adults, aged 25.9 ± 9.4 yrs and 85% were female. Blood levels of leucine, α-KIC, and HMB were extracted and log-transformed. Associations of leucine, α-KIC, and HMB with age, carotid-femoral pulse wave velocity (cfPWV), and intima-media thickness (IMT) were determined by pairwise correlations. A p -value smaller than 0.05 was considered significant. Results: Among 65 subjects with an age range of 13 to 45 yrs, older age was associated with lower levels of HMB (r=-0.37, P =0.002) and α-KIC (r=-0.30, P =0.016), but not leucine (r=-0.22, P =0.078). Higher levels of HMB and α-KIC, but not leucine, were associated with lower cfPWV (HMB: r=-0.33, P =0.010; α-KIC r=-0.31, P =0.018). Metabolites in the Leu/α-KIC/HMB metabolism pathway were also inversely associated with IMT, but only HMB showed a borderline statistical significance (r=-0.23, P =0.072). Conclusions: Our findings indicated a potential role of Leu/α-KIC/HMB metabolism in vascular aging, even in a young black population.