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.
The health benefit through the control of lipid levels in hyperlipidaemic individuals is evident from a large number of studies. The pharmacological options to achieve this goal shall be as specific and personalized as the reasons for and co-factors of hyperlipidaemia. It was the goal of this study to reveal the impact of leoligin on cholesterol levels and to define its mechanism of action. Oral application of leoligin in ApoE-/- mice led to significantly reduced total serum cholesterol levels and a reduction in postprandial blood glucose peak levels. In the absence of biochemical signs of toxicity, leoligin treatment resulted in reduced weight gain in mice. The effects of leoligin on serum cholesterol levels may be due to a direct inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) by a unique, non-statin-like binding mode. Postprandial serum glucose peaks may be reduced by a mild peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonistic activity of leoligin. No effect on atherosclerotic plaque size was observed. As a non-toxic, cholesterol-, peak glucose-, and weight gain-lowering compound, leoligin continues to fulfil characteristics of a potential agent for the treatment of cardiovascular disease (CVD). The counterregulatory overexpression of hepatic HMGCR in leoligin treated animals possibly explains the missing permanent anti-atherosclerotic effect.
The data presented in this study emphasizes the importance of SMCs in TAA development. Furthermore, our results provide evidence that the state of SMCs in the BAV-TAA (senescent) and TAV-TAA (pro-proliferative) differs significantly. For the first time, we also present findings that may argue for the occurrence of a viral infection in BAV-TAA SMCs.
Three-dimensional (3D) printing of vascular structures is of special interest for procedure simulations in Interventional Radiology, but remains due to the complexity of the vascular system and the lack of biological tissue mimicking 3D printing materials a technical challenge. In this study, the technical feasibility, accuracy, and usability of a recently introduced silicone-like resin were evaluated for endovascular procedure simulations and technically compared to a commonly used standard clear resin. Fifty-four vascular models based on twenty-seven consecutive embolization cases were fabricated from preinterventional CT scans and each model was checked for printing success and accuracy by CT-scanning and digital comparison to its original CT data. Median deltas (Δ) of luminal diameters were 0.35 mm for clear and 0.32 mm for flexible resin (216 measurements in total) with no significant differences (p > 0.05). Printing success was 85.2% for standard clear and 81.5% for the novel flexible resin. In conclusion, vascular 3D printing with silicone-like flexible resin was technically feasible and highly accurate. This is the first and largest consecutive case series of 3D-printed embolizations with a novel biological tissue mimicking material and is a promising next step in patient-specific procedure simulations in Interventional Radiology.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.