Nicotine Administration Augments Abdominal Aortic Aneurysm Progression in Rats

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Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal
aortic aneurysms (AAAs). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory
pathway (CAP). Thus, we hypothesize that low-dose nicotine impairs the progression of elastaseinduced AAAs in rats by exerting anti-inflammatory and anti-oxidative stress properties. Male
Sprague–Dawley rats underwent surgical AAA induction with intraluminal elastase infusion. We
compared vehicle rats with rats treated with nicotine (1.25 mg/kg/day), and aneurysm progression
was monitored by weekly ultrasound images for 28 days. Nicotine treatment significantly promoted
AAA progression (p = 0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloproteinase (pro-MMP) 2 (p = 0.029) and MMP9 (p = 0.030)
activity in aneurysmal tissue. No significant difference was found in the elastin content or the score
of elastin degradation between the groups. Neither infiltrating neutrophils nor macrophages, nor
aneurysmal messenger RNA (mRNA) levels of pro- or anti-inflammatory cytokines, differed between
the vehicle and nicotine groups. Finally, no difference in mRNA levels of markers for anti-oxidative
stress or the vascular smooth muscle cells’ contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased myristoylated
alanine-rich C-kinase substrate and proteins, in ontology terms, inflammatory response and reactive
oxygen species, and in contradiction to augmented AAAs. In conclusion, nicotine at a dose of
1.25 mg/kg/day augments AAA expansion in this elastase AAA model. These results do not support
the use of low-dose nicotine administration for the prevention of AAA progression.
Udgave nummer5
Antal sider19
StatusUdgivet - 10. maj 2023


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