Combination of Cadmium and High Cholesterol Levels as a Risk Factor for Heart Fibrosis

Abstract

The deleterious effects of increased cadmium (Cd) serum levels on the cardiovascular system are proven by epidemiological and basic science studies. Cd exposure of animals and humans is known to impair myocardial function, possibly leading to heart failure. This study aims at investigating the effect of Cd treatment on the cardiac system with emphasis on the combined effect of Cd and high serum cholesterol levels as an important cardiovascular risk factor. Detailed analyses of Cd-induced effects on the heart of ApoE-/- mice fed a high fat diet (HFD), ApoE-/- mice fed a normal diet (ND), and C57BL/6J mice fed a ND revealed proinflammatory and fibrotic changes in the presence of cellular hypertrophy but in the absence of organ hypertrophy. Hypercholesterolemia in ApoE-/- mice alone and in combination with Cd treatment resulted in significant cardiomyocyte cell death. Based on further analyses of heart sections, we conclude that severe hypercholesterolemia in combination with ApoE-/- genotype as well as Cd treatment results in necrotic cardiomyocyte death. These data were supported by in vitro experiments showing a Cd-induced depolarization of the mitochondrial membrane and the permeabilization of the plasma membrane arguing for the occurrence of Cd-induced necrotic cell death. In summary, we were able to show for the first time that the combination of high cholesterol and Cd levels increase the risk for heart failure through cardiac fibrosis. This observation could in part be explained by the dramatically increased deposition of Cd in the hearts of ApoE-/- mice fed a HFD.

Chemical imaging and assessment of cadmium distribution in the human body

“…[30][31][32] The interconnection between high serum cholesterol levels, which multiply Cd deposition in kidney and myocardium observed in mice, may also be of interest. 33 In our study, donors 3 and 4 had high levels of cholesterol (223 and 257 mg dl À1 , respectively). However, Cd concentration in heart muscle (21.8 and 46.4 mg kg À1 , respectively) and kidney cortex (7300 and 6280 mg kg À1 , respectively) as well as total Cd in the respective tissues (see next section, Fig.…”

“…caused by nutritional behaviours, physical inactivity, or ageing) adipose tissue turns into one of the biggest Cd pools of the entire body as already observed in our study for the obese donors 1 and 3 compared to the non-obese individuals 2 and 4. In addition, humans develop signs of Cd related diseases already at many-fold lower concentrations compared to mice and rats, 33 indicating the importance to focus on tissue with low concentrations of Cd in human studies.…”

Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

“…Chronic exposure to cadmium has been demonstrated to lead to hepatocyte damage [ 8 ]. Cadmium is an element of high toxicity and long half-life, which has negative effects on reproductive capacities and the cardiovascular system [ 9 ]. In humans, cadmium exerts carcinogenic effects affecting numerous cellular and molecular mechanisms (including redox imbalance, DNA repair, and inhibition of apoptosis) [ 10 ].…”

Vein graft thrombi, a niche for smooth muscle cell colonization – a hypothesis to explain the asymmetry of intimal hyperplasia

“…Sample preparation, immunohistochemical staining and immunofluorescence‐based staining on vein grafts (perianastomotic area) and quantification of signal intensity and cell numbers was performed as described in Data S1. For further details, see .…”

“…Hematoxylin and eosin (HE) staining, immunohistochemical staining and immunofluorescence-based evaluation of venous bypass graft sections Sample preparation, immunohistochemical staining and immunofluorescence-based staining on vein grafts (perianastomotic area) and quantification of signal intensity and cell numbers was performed as described in Data S1. For further details, see [20].…”