Nicotine Regulates Segmental Aortic Stiffening

Abstract

Introduction: Vascular stiffness and aortic stiffness in particular contributes to the development of AAA. Differential segment-specific stiffness development, quantified via the “segmental aortic stiffness (SAS)”- gradient, in adjacent segments may be a major contributor. Nicotine is the major risk factor for AAA development. This study investigates how nicotine influences stiffness development in the abdominal (AS) and thoracic (TS) segment. Methods: Wildtype-mice (C57BL/6) were infused with nicotine for 40 days using osmotic mini pumps (20mg/KG/day). Segmental aortic stiffness was analyzed using M-mode and pulse-wave velocity (PWV) ultrasound measurements. Thereafter, explanted aortae were used for myograph measurements and stiffness-related gene expression (Matrix-Metalloproteinase (MMP)-2, MMP-9, Col1A1, Col3A1) was analyzed. Results: Aortic PWV increased with nicotine (p<.05). In particular, stiffening for the AS occurred after 10 days (p<.05), while increase in aortic stiffness for the TS was only found after 40 days (p<.05). SAS was enhanced with nicotine vs. PBS for both time points. Stiffness-related genes were up-regulated after 40 days in both segments (p<.05). Discussion: Aortic stiffening is different for the TS and AS over a 40-day time course. SAS is enhanced with nicotine infusion based on stiffness-related gene expression. The TS has a higher capacity to withstand aortic stiffening, although the reason remains uncertain. Differences in stiffness development for the TS and AS may in part explain nicotine’s role in promoting AAA.