PMID- 31313498
OWN - NLM
STAT- MEDLINE
DCOM- 20191122
LR  - 20210110
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Print)
IS  - 1520-4081 (Linking)
VI  - 34
IP  - 10
DP  - 2019 Oct
TI  - Persistent organic pollutants (POPs) increase rage signaling to promote 
      downstream cardiovascular remodeling.
PG  - 1149-1159
LID - 10.1002/tox.22817 [doi]
AB  - Exposure to environmental contaminants and consumption of a high, saturated fatty 
      diet has been demonstrated to promote precursors for metabolic syndrome 
      (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this 
      study was to determine if exposure to the most prevalent environmental persistent 
      organic pollutants (POPs) would act as causative agents to promote metabolic 
      syndrome independent of dietary intake. We hypothesized that POPs will activate 
      the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling 
      cascade to promote downstream signaling modulators of cardiovascular remodeling 
      and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and 
      diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 
      6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken 
      for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade 
      via POPs exposure resulted in elevated levels of fibroblast differentiation 
      (alpha-smooth muscle actin) and RAGE expression indicated maladaptive cardiac 
      remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 
      (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a 
      result of POPs treatment to reduce innate cardioprotective mechanisms. In 
      comparison, ventricular collagen levels were decreased in mice exposed to POPs. 
      In conclusion, exposure to organic environmental pollutants may intensify 
      oxidative and inflammatory stressors to overwhelm protective mechanisms allowing 
      for adverse cardiac remodeling.
CI  - (c) 2019 The Authors. Environmental Toxicology published by Wiley Periodicals, Inc.
FAU - Coole, Jackson B
AU  - Coole JB
AD  - Department of Biological Sciences, College of Arts and Sciences, Mississippi 
      State University, Starkville, Mississippi.
FAU - Burr, Stephanie S
AU  - Burr SS
AD  - Department of BioMolecular Sciences, School of Pharmacy, University of 
      Mississippi, Oxford, Mississippi.
FAU - Kay, Amber M
AU  - Kay AM
AD  - Department of BioMolecular Sciences, School of Pharmacy, University of 
      Mississippi, Oxford, Mississippi.
FAU - Singh, Jaime A
AU  - Singh JA
AD  - Virginia Commonwealth University Health Systems, Richmond, Virginia.
FAU - Kondakala, Sandeep
AU  - Kondakala S
AD  - Department of Basic Sciences, College of Veterinary Medicine, Mississippi State 
      University, Starkville, Mississippi.
FAU - Yang, Eun-Ju
AU  - Yang EJ
AD  - Department of Basic Sciences, College of Veterinary Medicine, Mississippi State 
      University, Starkville, Mississippi.
FAU - Kaplan, Barbara L F
AU  - Kaplan BLF
AD  - Department of Basic Sciences, College of Veterinary Medicine, Mississippi State 
      University, Starkville, Mississippi.
FAU - Howell, George E 3rd
AU  - Howell GE 3rd
AD  - Department of Basic Sciences, College of Veterinary Medicine, Mississippi State 
      University, Starkville, Mississippi.
FAU - Stewart, James A Jr
AU  - Stewart JA Jr
AUID- ORCID: 0000-0001-8920-8809
AD  - Department of BioMolecular Sciences, School of Pharmacy, University of 
      Mississippi, Oxford, Mississippi.
LA  - eng
GR  - Mississippi State University Department of Biological Sciences/
GR  - Mississippi State University Shackoul's Honors College/
GR  - Office of Research and Graduate Studies at the Mississippi State University 
      College of Veterinary Medicine/
GR  - University of Mississippi School of Pharmacy/
GR  - Department of BioMolecular Sciences/
PT  - Journal Article
DEP - 20190716
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 0 (Environmental Pollutants)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/etiology/genetics/*metabolism/pathology
MH  - Environmental Pollutants/*adverse effects
MH  - Female
MH  - Glycation End Products, Advanced/metabolism
MH  - Heart/drug effects
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Obese
MH  - Myocardium/metabolism/pathology
MH  - Oxidative Stress/drug effects
MH  - Receptor for Advanced Glycation End Products/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Superoxide Dismutase/metabolism
PMC - PMC6771979
OTO - NOTNLM
OT  - AGE-RAGE signaling
OT  - heart
OT  - oxidative stress
OT  - persistent organic pollutants
OT  - type 2 diabetes mellitus
EDAT- 2019/07/18 06:00
MHDA- 2019/11/23 06:00
PMCR- 2019/10/01
CRDT- 2019/07/18 06:00
PHST- 2019/01/10 00:00 [received]
PHST- 2019/06/14 00:00 [revised]
PHST- 2019/06/26 00:00 [accepted]
PHST- 2019/07/18 06:00 [pubmed]
PHST- 2019/11/23 06:00 [medline]
PHST- 2019/07/18 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - TOX22817 [pii]
AID - 10.1002/tox.22817 [doi]
PST - ppublish
SO  - Environ Toxicol. 2019 Oct;34(10):1149-1159. doi: 10.1002/tox.22817. Epub 2019 Jul 
      16.