Nicotine administration augments abdominal aortic aneurysm progression in rats

ABSTRACT: Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAA). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesized that low-dose nicotine, an α7nAChR agonist, impairs the progression of AAAs in rats by activating the CAP. 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 the aneurysm progression was monitored by weekly ultrasound images for 28 days. Nicotine significantly promoted AAA progression after 28 days of treatment (p=0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloprotease (pro-MMP) 2(p=0.029) and MMP9(p=0.030) activity in aneurysmal tissue. No significant difference was found in 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 group. Finally, no difference in mRNA levels of markers for antioxidative stress or vascular smooth muscle cells contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased proteins in the ontology terms inflammation and reactive oxygen species and in contradiction to augmented AAAs. In conclusion, treatment with the given nicotine dose augmented AAA progression in this rat model.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Aorta

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Hans Christian Beck  

LAB HEAD: Hans Christian Beck

PROVIDER: PXD040414 | Pride | 2023-07-20

REPOSITORIES: Pride