title: Elevated concentrations of serum matrix metalloproteinase-2 and -9 and their associations with circulating markers of cardiovascular diseases in chronic arsenic-exposed individuals.
abstract: BACKGROUND
  Cardiovascular 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Serum 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 (r s  = 0.208, p < 0.001 for MMP-2; r s  = 0.163, p < 0.01 for MMP-9), hair (r s  = 0.163, p < 0.01 for MMP-2; r s  = 0.173, p < 0.01 for MMP-9) and nail (r s  = 0.160, p < 0.01 for MMP-2; r s  = 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.|Department of Applied Nutrition and Food Technology, Islamic University, Kushtia-7003, Bangladesh.
authors.forename: Md Shofikul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Nayan Chandra
authors.initials: NC
authors.lastname: Mohanto
authors.affiliation: Department of Applied Nutrition and Food Technology, Islamic University, Kushtia-7003, Bangladesh.
authors.forename: Md Rezaul
authors.initials: MR
authors.lastname: Karim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Sharmin
authors.initials: S
authors.lastname: Aktar
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Md Mominul
authors.initials: MM
authors.lastname: Hoque
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Atiqur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Momotaj
authors.initials: M
authors.lastname: Jahan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Rabeya
authors.initials: R
authors.lastname: Khatun
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Abdul
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.|Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Kazi Abdus
authors.initials: KA
authors.lastname: Salam
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
authors.forename: Zahangir Alam
authors.initials: ZA
authors.lastname: Saud
authors.affiliation: Kaliganj Upazila Health Complex, Gazipur, Dhaka, Bangladesh.
authors.forename: Mostaque
authors.initials: M
authors.lastname: Hossain
authors.affiliation: Systems Biology Research Centre, School of Bioscience, University of Skövde, Skövde, Sweden.
authors.forename: Aminur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Systems Biology Research Centre, School of Bioscience, University of Skövde, Skövde, Sweden.
authors.forename: Abul
authors.initials: A
authors.lastname: Mandal
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyataka
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Himeno
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh. khossainbio@gmail.com.
authors.forename: Khaled
authors.initials: K
authors.lastname: Hossain
mesh_terms: D000293:Adolescent; D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D001459:Bangladesh / Q000453:epidemiology; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D001151:Arsenic