Search

Background Peripheral arterial disease (PAD) is estimated to affect 7% of the adult population in the United States; however, there is currently little understanding of the key cellular and molecular pathways at play. With PAD characterized by vascular inflammation and associated calcification, the current study set out to elucidate the role of NLRP3 (nucleotide oligomerization domain‐like receptor family, pyrin domain containing 3) inflammasome activation in the current cohort. Methods and Results Global proteomics of human vessels with and without PAD from a total of 14 donors revealed an increase of proinflammatory associated ontologies, specifically acute phase and innate immunity. Targeted mass spectrometry showed a significant increase in NLRP3, confirmed by NLRP3 ELISA. Histological analysis from the same patients demonstrated expression of NLRP3, colocalizing in immunoreactive CD68 (cluster of differentiation 68) and CD209 (cluster of differentiation 209) macrophages. Moreover, transmission electron microscopy showed the locality of macrophage‐like cells in the presence of calcification, with confocal microscopy further validating the localization of CD68, NLRP3, and calcification via near‐infrared calcium tracer. Systemic inflammation and the presence of the NLRP3 inflammasome was assessed via flow cytometry and ELISA, respectively. Compared with patients without PAD, NLRP3 expression was significantly increased in serum. In addition, proinflammatory cytokine presence was significantly increased in disease versus control, with IL (interleukin)‐1β, TNF‐α (tumor necrosis factor α), and IL‐33 demonstrating the greatest disparity, correlating with NLRP3 activation. Conclusions The current findings demonstrate a link between NLRP3, macrophage accumulation, and calcification in arteries of patients with PAD, suggesting an association or possible driver of PAD in these patients.

Soccer athletes frequently experience repetitive head impacts (RHI) during games and practices, which may affect neural integrity over time and lead to altered brain structure. Neck strength is hypothesized to limit the transfer of force to the brain and decrease the effect of RHI on brain structure. The goal of our work was to examine whether greater neck strength is associated with more intact white matter organization (WMO) in collegiate athletes exposed to RHI. Collegiate soccer (n?=?17) and limited/non-contact sport (n?=?39) athletes were assessed prior to their athletic seasons. Participants completed neck strength assessments using handheld dynamometry in six test positions and diffusion tensor imaging. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated for 20 white matter (WM) regions. A multi-variate approach was used to examine the relationship between neck strength and diffusion measures in soccer and limited/non-contact athletes. Neck strength was positively associated with FA and negatively associated with RD across several WM regions in soccer players only. Neck strength was not significantly associated with MD or AD in either group. Greater neck strength was related to more intact WMO in athletes with high exposure to RHI, particularly in regions prone to damage from brain trauma such as the basal ganglia, superior longitudinal fasciculus, and frontoparietal WM. Future studies should examine neck strength as a factor to moderate neural outcomes in athletes with exposure to RHI.