Arterial Shear Rate Spectra Associate With Atheroprotection And Are Regulated By Vascular Resistance

PURPOSE: Endothelial cell culture preparations exposed to pulsatile shear patterns exhibit an atheroprotective phenotype with a positive association between increasing contribution from lower-frequency shear harmonics and increased markers of atheroprotection. The analogous relationship has yet to be established in humans. We therefore evaluated associations between arterial shear rate (SR) waveform spectra and endothelial function [brachial artery flow-mediated dilation (%FMD)] in young healthy humans. METHODS: We used linear regression to explore associations between the most dominant harmonics from arterial SR waveforms and functional measures such as %FMD. Feature selection from ancillary participant data was used to identify candidate mechanisms that regulate spectral characteristics of arterial waveforms. A second, and independent sample of humans was recruited and exposed to local forearm heating and cooling to test the regulating influence of vascular resistance on upstream harmonic profiles. A third set of participants were exposed to exercise and the eliciting arterial waveform profiles were characterized using spectral decomposition. RESULTS: The absolute amplitudes of the first (r = 0.46, P < 0.01) and second (r = 0.48, P < 0.001) SR harmonics associated with greater %FMD. Peripheral resistance was suggested as a relevant feature that regulated spectral characteristics of the arterial SR waveform. Decreasing peripheral resistance using local forearm heating increased spectral shear amplitudes from lower-frequency harmonics (second harmonic, P < 0.01; and third harmonic, P < 0.01). Increased low frequency shear spectra (first harmonic, P < 0.01; second harmonic, P < 0.01) was also observed concomitant with decreases in peripheral resistance during moderate-intensity aerobic exercise on a cycle ergometer. CONCLUSIONS: Leftward shifts in conduit artery SR spectra are regulated by vascular resistance and associate with atheroprotection, likely via endothelial shear sensing. Supported by: Natural Sciences and Engineering Research Council of Canada