Sirt1 during childhood is associated with microvascular function later in life

摘要

Rodriguez-Miguelez P, Looney J, Thomas J, Harshfield G, Pollock JS, Harris RA. Sirtl during childhood is associated with microvascular function later in life. Am J Physiol Heart Circ Physiol 318: H1371-H1378, 2020. First published April 24, 2020; doi: 10.1152/ajpheart.00024.2020.—Microvascular dysfunction often precedes other age-related macrovascular conditions and predicts future cardiovascular risk. Sirtuin 1 (Sirtl) has recently emerged as a protein that protects the vasculature and reduces the risk of cardiovascular diseases. We tested the hypothesis that lower Sirtl during childhood is associated with a reduced microvascular function during adulthood. Thirty-four adults (34 ± 3 yr) from the Augusta Heart Study returned to participate in the present clinical observational study. Sirtl was assessed in samples collected during both adulthood and participants' childhood (16 ± 3 yr), and data were divided based on childhood Sirtl concentrations: <3 ng/dL (LowCS; n = 16) and ≥3 ng/dL (HighCS; n = 18). MVF was evaluated in all of the adults using laser-Doppler flowmetry coupled with three vascular reactivity tests: 1) local thermal hyperemia (LTH), 2) post-occlusive reactive hyper-emia (PORH), and 3) iontophoresis of acetylcholine (ACh). The hyperemic response to LTH was significantly (P ≤ 0.044) lower in the LowCS than in the HighCS group. Similarly, the LowCS also exhibited an ameliorated (P ≤ 0.045) response to the PORH test and lower (P≤ 0.008) vasodilation in response to iontophoresis of ACh when compared with the HighCS. Positive relationships were identified between childhood Sirtl and all MVF reactivity tests (r≥0.367, P ≤ 0.004). Novel observations suggest that lower Sirtl during childhood is associated with premature microvascular dysfunction in adulthood. These findings provide evidence that Sirtl may play a critical role in microvascular function and have therapeutic potential for the prevention of age-associated vascular dysfunction in humans. NEW NOTEWORTHY With a longitudinal cohort, novel observations from the present study demonstrate that individuals who had lower Sirtl early in life exhibit premature microvascular dysfunction during adulthood and may be at higher risk to develop CVD. These results provide experimental evidence that Sirtl may play an important role in microvascular function with age and represent a potential therapeutic target to prevent premature vascular dysfunction.