Metals bioaccumulation in carotid atheromatous plaques and their potential role in atherosclerosis occurrence

The WHO estimates that 24% of all deaths worldwide – amounting to 12.6 million people – are due to environmental risks. Pollution by toxic metals stand as a public health risk around the world. Toxic metals include heavy metals and other metal compounds which can negatively affect public health in the milieu of noncommunicable diseases, including cardiovascular diseases. However, few studies investigated the accumulation of toxic metals in the carotid plaque. Starting from this consideration, in the present study both carotid atheromatous plaques (n=24) and thrombotic samples (n=60) have been analysed through spectroscopic technologies to detect the presence of trace elements (TE) including Aluminium (Al), Arsenic (As), Cadmium (Cd), Mercury (Hg) and Lead (Pb). Al and Pb were detected in all samples, with Al as the most abundant element. Cd was detected in 79% of samples and its concentration correlated with instability of the plaques. We further investigate the possible cumulative effects of these elements on vulnerability of the plaques, finding that the majority of unstable plaques were characterized by at least 3 metals. To determine which could be the mechanisms underlying the increased vulnerability associated to the cumulative effects of these toxicants, we performed immunohistochemistry evaluation on inflammatory markers, cell death (apoptosis and NETosis) and collagen deposition. However, none of these processes was associated with cumulative effects, which probably activates more complex mechanisms that lead to vulnerable plaques. To assess the site of bioaccumulation of these metals, atheromatous plaques underwent SEM and TEM EDX analysis, which allowed the detection of Al within 12 of 57 samples. However, no other metals were detected due to the very high Al concentration. Moreover, we also investigated samples of thrombi for Al, Cd, Pb, Nickel (Ni) and Chromium VI (CrVI), finding higher concentration of the common metals compared to atheromatous plaques, probably due to increased concentration of the metals within blood. All together these findings suggests that toxic metals could accumulate simultaneously thus generating a cumulative effect capable to destabilize the carotid plaques. Future study will assess how these metals could promote vulnerability of atheromatous plaques in humans.