Arsenic-Induced Decreases in the Vascular Matrix

Abstract

Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five, or eight weeks. At five and eight weeks, RNA from the lungs of control and AsIII-exposed animals was processed for microarray. Sixty-five genes were significantly and differentially expressed. Differential expression of extracellular matrix (ECM) gene transcripts was particularly compelling, as 91% of genes in this category, including elastin and collagen, were significantly decreased. In additional experiments, real-time RT-PCR showed an AsIIIinduced decrease in many of these ECM gene transcripts in the heart and NIH3T3 fibroblast cells. Histological stains for collagen and elastin show a distinct disruption in the ECM surrounding small arteries in the heart and lung of AsIII-exposed mice. Immunohistochemical detection of α-smooth muscle actin in blood vessel walls was decreased in the AsIII-exposed animals. These data reveal a functional link between AsIII exposure and disruption in the vascular ECM. These AsIII-induced early pathological events may predispose humans to respiratory and cardiovascular diseases linked to chronic low-dose AsIII exposure.

Health effects and arsenic species in urine of copper smelter workers

“…[42,43] CC16 anti-inflammatory properties are supported by the fact that the depletion of the CC16 pool in the lung is accompanied by increased concentration of As(+3), the forms responsible for respiratory diseases. [44] As(+3) correlated with the increased serum iron (Fe-S) concentration. Fe-S goes hand-in-hand with an increase in LDH activity, a marker of lung injury in the inflammatory process.…”

Cardiovascular effects of arsenic: clinical and epidemiological findings

“…Polymorphisms in the genes of enzymes involved in As metabolism, especially As methyltransferase, and in redox enzymes can modulate As toxicity and its CV effects (Vahter 2000;Hsueh et al 2005;States et al 2009;Hsieh et al 2011;Hughes et al 2011) Reduced synthesis of extracellular matrix and damage to vascular smooth muscle cells are other mechanisms that could promote atherosclerotic plaque formation and instability (Hays et al 2008;, while oxidation of lipids would make them more prone to be internalized in the vessel wall ). As appears to enhance platelet aggregation (Lee et al 2002), possibly by exposing phosphatidylserine (Bae et al 2009) though studies are conflicting (Lin et al 2010), and reduces endothelial fibrinolytic activity by reducing t-PA and increasing PAI-1 level and activity (Jiang et al 2002), and reduces synthesis of proteoglycans such as heparan sulfate (Fujiwara et al 2005).…”

Arsenic induces sustained impairment of skeletal muscle and muscle progenitor cell ultrastructure and bioenergetics

“…The niche is dynamic and characterized by the presence of autocrine and paracrine factors, as well as extracellular matrix proteins. Chronic As(III) exposure has been associated with modulation of tissue microenvironment as characterized by a modification of matrix components (11), aberrant angiogenesis and vessel remodeling (12, 13), and increased fibrosis (14, 15). In vivo (9) and in vitro (10) studies demonstrate a dose-dependent As(III) impairment of muscle regeneration, decreased myotube formation from isolated myoblasts and decreased activation of the myogenic molecular program (10).…”