The Vascular System as a Target of Metal Toxicity

Abstract

Vascular system function involves complex interactions among the vascular endothelium, smooth muscle, the immune system, and the nervous system. The toxic metals cadmium (Cd), arsenic (As), and lead (Pb) can target the vascular system in a variety of ways, ranging from hemorrhagic injury to subtle pathogenic remodeling and metabolic changes. Acute Cd exposure results in hemorrhagic injury to the testis, although some strains of animals are resistant to this effect. A comparison of Cd-sensitive with Cd-resistant mouse strains showed that expression of the Slc39a8 gene, encoding the ZIP8 transporter, in the testis vasculature endothelium is responsible for this difference. Endogenously, ZIP8 is a Mn(2+)/HCO(3)(-)symporter that may also contribute to Cd damage in the kidney. Chronic Cd exposure is associated with various cardiovascular disorders such as hypertension and cardiomyopathy and it is reported to have both carcinogenic and anticarcinogenic activities. At noncytotoxic concentrations of 10-100nM, Cd can inhibit chemotaxis and tube formation of vascular endothelial cells. These angiostatic effects may be mediated through disruption of vascular endothelial cadherin, a Ca(2+)-dependent cell adhesion molecule. With regard to As, ingestion of water containing disease-promoting concentrations of As promotes capillarization of the liver sinusoidal endothelium. Because capillarization is a hallmark precursor for liver fibrosis and contributes to an imbalance of lipid metabolism, this As effect on hepatic endothelial cells may be a pathogenic mechanism underlying As-related vascular diseases. With regard to Pb, perinatal exposure may cause sustained elevations in adult blood pressure, and genetically susceptible animals may show enhanced sensitivity to this effect. Taken together, these data indicate that the vascular system is a critical target of metal toxicity and that actions of metals on the vascular system may play important roles in mediating the pathophysiologic effects of metals in specific target organs.

Lead, Smoking, and Peripheral Vascular Function

“…4 In addition, in human lymphocytes, elevated lead concentrations with protein denaturation were also found in our studies. 4 This is in concordance with the study from Prozialeck et al 5 showing the vascular system as a target of lead toxicity.…”

Relationship Between Blood Lead Level and Elevated Blood Pressure in Hypertensive Patients: Implication of Nitric Oxide

“…There is considerable public health interest in the possible toxic effects of environmental lead exposure on the cardiovascular system, with additional concern regarding the role of chronic low-level lead exposures in the pathogenesis of hypertension, a leading risk factor for cardiovascular disease morbidity and mortality [7,2]. Vupputuri et al, [22] suggested that increased levels of B-Pb remain an important environmental risk factor for elevated blood pressure.…”

“…It has been detected in all phases of environment and biological system. The persistence of lead in the blood of animals and humans and the associated health risk is a topic of current debate and concern [1,2]. Moreover, rapid industrialization and the continued use of leaded gasoline appear to be increasing lead exposure throughout the developing world [3].…”

“…Lead exposure may be more of a risk factor for certain ''susceptible populations'', and thus may not be apparent in the general population. Inasmuch as hypertension remains a significant risk factor for other forms of cardiovascular disease, the propensity for environmental exposure actors to contribute to this risk is, potentially, an important public health concern [2].…”

Oxidative Stress and Cardiovascular Dysfunction Associated with Cadmium Exposure: Beneficial Effects of Curcumin and Tetrahydrocurcumin

“…The most commonly affected organ systems are the kidney, lung, bone and skeletal, cardiovascular, and nervous systems (Jaishankar et al 2014). Observational studies indicate that chronic Cd exposure is associated with an increased risk of cardiovascular disease, including hypertension, atherosclerosis, nephropathy, and diabetes (Puri 1999;Satarug et al 2005;Eum et al 2008;Prozialeck et al 2008;Messner and Bernhard 2010;Alissa and Ferns 2011;ATSDR 2012;Satarug and Moore 2012).…”