Objectives-Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of atherosclerosis. Methods and Results-In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters(ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.6[1.1.-2.3], Pϭ0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm 2 , PϽ0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies. Conclusion-Our research suggests Cd has promoting effects on early human and murine atherosclerosis, which were partly offset by high Zn concentrations. Key Words: cadmium, zinc Ⅲ endothelial Ⅲ dysfunction Ⅲ injury Ⅲ permeability Ⅲ necrosis Ⅲ ApoE Ⅲ atherosclerosis Ⅲ vascular Ⅲ pathophysiology Ⅲ risk factor Ⅲ intima media thickness Ⅲ apoptosis Ⅲ cell death S ince the use of Cd in manifold industrial applications, sources for and the amount of Cd uptake by humans has increased dramatically. Cd is, for example, released into the air through the burning of fossil fuels (coal, oil) and the incineration of municipal waste (Environmental Protection Agency, 2000). The most relevant sources for Cd uptake by humans are, however, cigarette smoking (one cigarette contains Ϸ1 to 2 g; daily uptake of Cd Ϸ1 to 3 g per pack smoked) and food for nonsmokers (daily intake Ϸ30 g; daily uptake Ϸ1 to 3 g), as well as exhaust gases (Agency for Toxic Substances and Disease Registry, 1999). After inhalation or ingestion of Cd, it is transferred into the bloodstream (whole blood and serum Cd concentrations range between Ϸ0.2 and Ϸ20 nmol/L 1,2 ), where Cd is transported either as a free ion or protein-bound, eg, attached to albumin or metallothioneins. Cd is taken up by cells of Cd target organs (liver, kidneys, and testis) via solute carriers, calcium and manganese channels, and iron transporters. [3][4][5] In 2001, Abu-Hayyeh et al 6 demonstrated that the aortic vessel wall is another under-recognized target organ for Cd accumulation (aortic wall concentrations of Cd are up to 20 mol/ L). Epidemiologically, high Cd level was found to be associated with hypertension, stroke, and cardiac arrest, 7-9 but confirmatory data are sparse and the mechanistic basis for these interactions remains unclear. Houtman et al observed a higher than expected frequency of atherosclerosis in a...

BackgroundWhile several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as “good cholesterol”. Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted.MethodThis review article is based on a selective literature review.ResultsIn individuals without a history of cardiovascular events, low concentrations of HDL-C are inversely associated with the risk of future cardiovascular events. This relationship may, however, not apply to patients with metabolic disorders or manifest cardiovascular disease. The classical function of HDL is to mobilise cholesterol from extrahepatic tissues for delivery to the liver for excretion. These roles in cholesterol metabolism as well as many other biological functions of HDL particles are dependent on the number as well as protein and lipid composition of HDL particles. They are poorly reflected by the HDL-C concentration. HDL can even exert negative vascular effects, if its composition is pathologically altered. High serum HDL-C is therefore no longer regarded protective. In line with this, recent pharmacological approaches to raise HDL-C concentration have not been able to show reductions of cardiovascular outcomes.ConclusionIn contrast to LDL cholesterol (LDL-C), HDL-C correlates with cardiovascular risk only in healthy individuals. The calculation of the ratio of LDL-C to HDL-C is not useful for all patients. Low HDL-C should prompt examination of additional metabolic and inflammatory pathologies. An increase in HDL-C through lifestyle change (smoking cessation, physical exercise) has positive effects and is recommended. However, HDL-C is currently not a valid target for drug therapy.

The acute-phase protein SAA modifies the biological effects of HDL-C in several clinical conditions. The concomitant measurement of SAA is a simple, useful, and clinically applicable surrogate for the vascular functionality of HDL.

The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.