Non-Toxic Cadmium Concentrations Induce Vascular Inflammation and Promote Atherosclerosis

Abstract

Background: Cadmium is a potential new risk factor for early atherosclerosis and cardiovascular diseases in humans, yet pathogenetic mechanisms are still a matter of debate. Methods and Results:In-depth histological analysis of 18 sections taken from 6 cadmium-fed ApoE-/- mice and 12 sections from 5 litter-mates not exposed to cadmium by light and scanning electron microscopy was performed. Cadmium-fed mice showed a marked increase in lesion load (plaque area) and severity as classified according to the American Heart Association vascular lesion grading. All inflammatory markers studied (CD68, CD3, CD25, vascular cell adhesion molecule 1 (VCAM-1), and heat shock protein 60 (Hsp60)) yielded a higher expression in cadmium-fed mice. Statistical difference was achieved for VCAM-1 and Hsp60 (P=0.03 and P=0.02). The shoulder region of atherosclerotic plaques in cadmium-fed mice showed a prominent retraction of endothelial cells on electron microscopy. Conclusions:Our data indicate that cadmium exposure amplifies the development of vessel pathology in atherosclerosis susceptible ApoE-/- mice and suggests upregulation of VCAM-1 and Hsp60 and endothelial leakage as potential pathomechanisms. (Circ J 2011; 75: 2491 - 2495

Characterization and function analysis of Hsp60 and Hsp10 under different acute stresses in black tiger shrimp, Penaeus monodon

“…The highest PmHsp60 expression was significantly induced by cadmium exposure, in accordance with previous studies (Qian et al 2012). For example, the relative mRNA expression of LvHsp60 shows sensitive responses to cadmium exposure and reaches 21.9-fold that of the control group within 24 h. Similar phenomena have also been observed in mouse and chicken (Knoflach et al 2011;Chen et al 2012). These results suggest that Hsp60 may play an important role in cadmium tolerance and can be used as biomarker for cadmium pollution.…”

Tobacco Smoking Decreases Plasma Concentration of the Emerging Cardiovascular Risk Marker, L-homoarginine

“…Although both study groups (smokers and nonsmokers) were exposed to the same occupational conditions, the possible presence of other heavy metals (eg, zinc) in the work environment might have affected study parameters. 20, 23 There was no additional exposure to environmental tobacco smoke during work hours because there was a complete smoking ban at the work place. Another concern is related to the assessment of smoking habits, which were based only on a questionnaire and not on a more objective method, such as the measurement of cotinine in urine or plasma.…”

Cadmium Exposure and Incident Peripheral Arterial Disease

“…Mechanistic evidence has linked cadmium to atherosclerosis development, [4][5][6]36 and cross-sectional studies have also evidenced an increased prevalence of atherosclerotic vascular disease with increased cadmium exposure in the US general population 21,22 and in populations from other countries. 6,17,23 Our results add prospective evidence of the importance of cadmium exposure as a risk factor for the development of PAD.…”

“…[4][5][6]57 Cadmium could also act through epigenetic 58 and endocrine disruption [59][60][61] pathways. The mechanistic studies add biological plausibility to the evidence from studies in human populations, suggesting a doseresponse relationship in the association between cadmium exposure and PAD.…”

“…[1][2][3] Experimental models support that cadmium can induce atherosclerosis and vascular dysfunction in animal models. [4][5][6] Proposed mechanisms include upregulation of cytokines and cell adhesion molecules and increase of endothelial cell permeability and death. 7 Promotion of oxidative stress and hypertension-related mechanisms could also be involved.…”