Abstract
BackgroundCardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and −9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs.MethodsA total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits.ResultsSerum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (rs = 0.208, p < 0.001 for MMP-2; rs = 0.163, p < 0.01 for MMP-9), hair (rs = 0.163, p < 0.01 for MMP-2; rs = 0.173, p < 0.01 for MMP-9) and nail (rs = 0.160, p < 0.01 for MMP-2; rs = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (≤10, 10.1-50 and > 50 μg/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs.ConclusionsThis study showed the significant positive associations and dose–response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.
Highlights
Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality
This study showed the interactions of Matrix metalloproteinases (MMPs)-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the Matrix metalloproteinase-2 (MMP-2) and MMP-9 -mediated mechanism of arsenic-induced CVDs
We have previously investigated the associations of arsenic exposure with several circulating markers of CVDs such as high density lipoprotein cholesterol (HDL-C), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the same population group selected for this study [3]
Summary
Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs. Arsenic is a potent environmental pollutant and a well established human carcinogen. Chronic exposure to arsenic is associated with a variety of diseases such as cancers, dermatitis, CVDs, neurological disorders, diabetes mellitus, renal failure and liver dysfunction [1,2,3,4,5,6,7,8,9]. Exposure to arsenic through drinking water is a major threat to the public health in many countries especially in Bangladesh, India, Taiwan, China, Vietnam, Cambodia and Mongolia. Presence of excessive amount of arsenic in foods and vegetables indicate that exposure to arsenic is unavoidable
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