Selenium nanoparticles protect against abdominal aortic aneurysm: evidence from Mendelian randomisation and preclinical models
S Chen, X Gao, L Q Shao, X L Zhang, J C XiuAbstract
Background and Aims
Abdominal aortic aneurysm (AAA), a chronic inflammatory disease, is typically asymptomatic but carries life-threatening risks. Currently, there remains a lack of effective pharmacological therapies to inhibit AAA progression. Emerging evidence indicates that AAA patients exhibit reduced selenium levels in arterial tissues and plasma, which are negatively correlated with the maximum abdominal aortic diameter. As a key component of selenoproteins, selenium possesses prominent antioxidant and anti-inflammatory properties, which are highly consistent with the core pathological mechanisms of AAA. However, it remains unclear whether decreased selenium levels are a cause or a consequence of AAA progression. Whether selenium nanoparticles, a form of selenium with low toxicity and high bioactivity, can directly inhibit AAA progression and offer clinical translational advantages remains to be fully elucidated. Therefore, this study aimed to investigate the role of selenium nanoparticles in regulating AAA progression.
Methods and Results
For Mendelian randomisation, selenium summary-level data were from the IEU OpenGWAS Dataset (ieu-a-1077), and aortic aneurysm data from the FinnGen consortium (ICD-10 I71 diagnosis; sample sizes: 325,502 [aortic aneurysm], 321,100 [AAA], 325,220 [thoracic aortic aneurysm]). Combined with two well-established AAA mouse models (AngII-infused and PPE-induced) and selenium nanoparticle supplementation, our preliminary findings show a strong genetic association between low selenium levels and AAA susceptibility (OR = 0.78, P < 0.001). Transmission electron microscopy imaging showed that the selenium nanoparticles exhibited a sheet-like morphology. The negatively charged selenium nanoparticles (zeta potential approximately −39.73 mV) had an average hydrodynamic diameter of 290.9 nm, as determined by dynamic light scattering. After intravenous injection of selenium nanoparticles in mice (50 µg/kg, twice a week), the nanoparticles specifically localised to AAA lesions, were efficiently internalised by macrophages, and significantly reduced AAA incidence, aneurysm maximum diameter, and macrophage-mediated inflammation, with excellent biocompatibility.
Conclusions
Our results support selenium nanoparticles as a potential candidate for AAA treatment. By innovatively integrating Mendelian randomisation with selenium nanoparticle intervention, our study clarifies the causal link between selenium levels and AAA susceptibility while exploring its translational therapeutic potential. Moving forward, we will further elucidate the molecular mechanisms underlying the attenuation of AAA progression by selenium nanoparticles; we will also investigate the potential of selenium nanoparticles as a functional coating for vascular stents beyond conventional systemic administration, while systematically optimising their therapeutic doses to provide solid experimental evidence for clinical translation.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.