Abstract 465: Nicotine Differentially Influences Segmental Aortic Stiffening

Abstract

Background: Arterial stiffness is a major risk factor for various cardiovascular diseases and contributes to the development of abdominal aortic aneurysms (AAA). In this context, differential aortic stiffening of adjacent aortic segments increases aortic wall stress and accelerates the disease. Smoking is a major risk factor for AAA, in part due to nicotine. In this study, we investigated aortic stiffening of the thoracic and abdominal aorta and analyzed stiffness-related gene expression. Methods: 36 WT mice (C57BL/6) mice were infused with nicotine or PBS using osmotic mini pumps for 42 days. Thoracic segment (TS) and abdominal segment (AS) aortic stiffness were analyzed using ultrasound (M-Mode and PW). TS and AS were further investigated by ex vivo myograph measurements. Gene expression for TMIP2, MT1-MMP, MMP2, collagen type I and type III was performed for both segments separately. Results: Myograph measurements revealed increased strain within the AS after 2 weeks (p<.05) in response to nicotine (vs. PBS), but no stiffening of the TS. After 6 weeks, the AS showed additional increases in strain with nicotine (p<.05); however, only minor increases in stiffness could be observed for the TS. Ultrasound M-Mode results confirmed the myograph results. Nicotine treatment also led to increased aortic pulse wave velocity (PWV) after 2 weeks (p<.05) and 6 weeks (p<.05). Gene expression analysis revealed up-regulation in the TS and AS of MT1-MMP and MMP2 after 2 weeks of nicotine, while TIMP2 was downregulated, and collagen type I and type III were up-regulated in both TS and AS (p<.05). After 6 weeks, there were no longer significant differences in either segment for any of these genes. Discussion: Aortic stiffening in response to nicotine varies between the TS and AS segment over a time course of 6 weeks. This leads to an increased stiffness gradient between the TS and AS. Gene expression changes in stiffness-related genes occurred in response to nicotine, although no difference appeared between the segments. We conclude that the difference in stiffness development for TS and AS could be based on a different basic morphological structure involving elastin and collagen load, and that these responses may in part explain nicotine’s role in promoting AAA.