Trace Elements and Paraoxonase-1 Activity in Lower Extremity Artery Disease

Joaquim Rovira, Anna Hernández-Aguilera, Fedra Luciano-Mateo, Noemí Cabré, Gerard Baiges-Gaya, Martí Nadal, Vicente Martín-Paredero, Jordi Camps, Jorge Joven, José L. Domingo

Oxidative stress and inflammation are candidate mechanisms to explain the potential role of exposure to metals and reduced activity of paraoxonase-1 (PON1) in age-related diseases. Both may be risk factors contributing to atherosclerosis. In the present study, inductively coupled mass spectrometry was used to explore multiple trace elements, while in-house methods were employed to measure PON1-related variables in patients with lower extremity artery disease (LEAD). Healthy controls were matched for sex, age, body weight, and relevant genotype variants. Serum concentrations of As, Ba, Cu, and Sr were higher in patients than those in controls, with a strong predictive ability to discriminate between groups. Differences in serum Pb, Cd, and Zn were negligible. Serum Cu increased when the disease was more severe, but a negative trend was noted for serum As, B, Ba, and Zn. The only variable associated with ankle-brachial index was serum Zn. Serum PON1 activity was significantly lower in LEAD patients. When the ability of serum trace elements to modulate PON1 activity was explored, the analysis revealed a unique association with serum Zn. The current results strongly suggest that Zn may have a protective effect in non-coronary atherosclerosis and indicate that this element may exert its anti-inflammatory and antioxidant functions through interactions with PON1 activity. These findings deserve confirmation and further research. In particular, the periodic evaluation of serum trace elements and the prescription of Zn supplements are easy measures to implement and that can improve the treatment of patients with LEAD.