PMID- 35676585
OWN - NLM
STAT- MEDLINE
DCOM- 20221021
LR  - 20221021
IS  - 1614-7499 (Electronic)
IS  - 0944-1344 (Linking)
VI  - 29
IP  - 51
DP  - 2022 Nov
TI  - Effects of heavy metals on cardiovascular diseases in pre and post-menopausal 
      women: from big data to molecular mechanism involved.
PG  - 77635-77655
LID - 10.1007/s11356-022-21208-8 [doi]
AB  - To assess the link between a mixed heavy metal (cadmium, lead, and mercury) and 
      the 10-year risk of cardiovascular diseases (CVDs) in pre- and post-menopausal 
      Korean women aged >/=20 years, as well as identify potential molecular mechanisms 
      of mixed heavy metal-induced CVDs. Multivariate linear regression, weighted 
      quantile sum (WQS) regression, quantile g-computation (gqcomp), and Bayesian 
      kernel machine regression (BKMR) models were used to examine the effects of mixed 
      heavy metals and the 10-year risk of CVDs. The Comparative Toxicogenomics 
      Database, MicroRNA ENrichment TURned NETwork, and the microRNA sponge generator 
      and tester were used as the key data-mining approaches. In our BKMR analysis, we 
      found that the overall effect of mixed heavy metals was linked to the 10-year 
      risk of CVDs in postmenopausal women in the upper 20(th) percentiles and in 
      premenopausal women in the upper 55(th) percentiles. Mercury was identified as 
      the key chemical for the 10-year risk of CVDs in pre- and postmenopausal women. 
      In silico analysis revealed that a heavy metal mixture interacted with six genes 
      associated with CVD development. Physical interactions (77.6%) were found to be 
      the most common among CVD-related genes induced by the heavy metals studied. 
      Several pathways have been identified as the main molecular mechanisms that could 
      be affected by studied heavy metals and are implicated in the development of CVDs 
      (e.g., lipid and lipoprotein metabolism, lipoprotein metabolism, cholesterol 
      metabolism, and cardiovascular disease). ALB, APOE, ATF5, and CREB3L3 were the 
      key genes and transcription factors related to CVDs induced by the mixture of the 
      investigated heavy metals, respectively. The two miRNAs with the highest 
      interaction and expression in the development of CVDs were hsa-miR-199a-5p and 
      hsa-miR-199a-3p. We also designed and tested miRNA sponge sequences for these 
      miRNAs. The cutoff thresholds for each heavy metal level linked with the 10-year 
      risk of CVDs were described. A mixture of heavy metal exposures, especially 
      mercury, was more strongly linked with the 10-year risk of CVDs in postmenopausal 
      women than in premenopausal women. Early interventions in postmenopausal women 
      should be considered to reduce CVD risks.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Nguyen, Hai Duc
AU  - Nguyen HD
AD  - Department of Pharmacy, College of Pharmacy and Research Institute of Life and 
      Pharmaceutical Sciences, Sunchon National University, Sunchon, 57922, Jeonnam, 
      Republic of Korea.
FAU - Kim, Min-Sun
AU  - Kim MS
AUID- ORCID: 0000-0001-9952-0038
AD  - Department of Pharmacy, College of Pharmacy and Research Institute of Life and 
      Pharmaceutical Sciences, Sunchon National University, Sunchon, 57922, Jeonnam, 
      Republic of Korea. minsun@scnu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20220609
PL  - Germany
TA  - Environ Sci Pollut Res Int
JT  - Environmental science and pollution research international
JID - 9441769
RN  - 00BH33GNGH (Cadmium)
RN  - 0 (Metals, Heavy)
RN  - FXS1BY2PGL (Mercury)
RN  - 0 (MicroRNAs)
RN  - 0 (Lipids)
RN  - 0 (Transcription Factors)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - 0 (Apolipoproteins E)
RN  - 0 (CREB3L3 protein, human)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Cardiovascular Diseases/epidemiology
MH  - Cadmium/analysis
MH  - Postmenopause
MH  - Bayes Theorem
MH  - Big Data
MH  - *Metals, Heavy
MH  - *Mercury/analysis
MH  - *MicroRNAs
MH  - Lipids
MH  - Transcription Factors
MH  - Cholesterol
MH  - Apolipoproteins E
MH  - Cyclic AMP Response Element-Binding Protein
OTO - NOTNLM
OT  - Cardiovascular diseases
OT  - Heavy metals
OT  - Molecular mechanisms
OT  - Pre and post menopause
EDAT- 2022/06/09 06:00
MHDA- 2022/10/22 06:00
CRDT- 2022/06/08 23:34
PHST- 2022/03/22 00:00 [received]
PHST- 2022/05/27 00:00 [accepted]
PHST- 2022/06/09 06:00 [pubmed]
PHST- 2022/10/22 06:00 [medline]
PHST- 2022/06/08 23:34 [entrez]
AID - 10.1007/s11356-022-21208-8 [pii]
AID - 10.1007/s11356-022-21208-8 [doi]
PST - ppublish
SO  - Environ Sci Pollut Res Int. 2022 Nov;29(51):77635-77655. doi: 
      10.1007/s11356-022-21208-8. Epub 2022 Jun 9.