PMID- 28386844
OWN - NLM
STAT- MEDLINE
DCOM- 20180709
LR  - 20181113
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 433
IP  - 1-2
DP  - 2017 Sep
TI  - Toll-like receptor 4 mediates vascular remodeling in hyperhomocysteinemia.
PG  - 177-194
LID - 10.1007/s11010-017-3026-9 [doi]
AB  - Although hyperhomocysteinemia (HHcy) is known to promote downstream 
      pro-inflammatory cytokine elevation, the precise mechanism is still unknown. One 
      of the possible receptors that could have significant attention in the field of 
      hypertension is toll-like receptor 4 (TLR-4). TLR-4 is a cellular membrane 
      protein that is ubiquitously expressed in all cell types of the vasculature. Its 
      mutation can attenuate the effects of HHcy-mediated vascular inflammation and 
      mitochondria- dependent cell death that suppresses hypertension. In this review, 
      we observed that HHcy induces vascular remodeling through immunological 
      adaptation, promoting inflammatory cytokine up-regulation (IL-1beta, IL-6, TNF-alpha) 
      and initiation of mitochondrial dysfunction leading to cell death and chronic 
      vascular inflammation. The literature suggests that HHcy promotes TLR-4-driven 
      chronic vascular inflammation and mitochondria-mediated cell death inducing 
      peripheral vascular remodeling. In the previous studies, we have characterized 
      the role of TLR-4 mutation in attenuating vascular remodeling in 
      hyperhomocysteinemia. This review includes, but is not limited to, the 
      physiological synergistic aspects of the downstream elevation of cytokines found 
      within the vascular inflammatory cascade. These events subsequently induce 
      mitochondrial dysfunction defined by excessive mitochondrial fission and 
      mitochondrial apoptosis contributing to vascular remodeling followed by 
      hypertension.
FAU - Familtseva, Anastasia
AU  - Familtseva A
AD  - Department of Physiology, School of Medicine, Health Sciences Centre, University 
      of Louisville, A-1215, 500, South Preston Street, Louisville, KY, 40202, USA.
FAU - Jeremic, Nevena
AU  - Jeremic N
AD  - Department of Physiology, School of Medicine, Health Sciences Centre, University 
      of Louisville, A-1215, 500, South Preston Street, Louisville, KY, 40202, USA. 
      n0jere01@louisville.edu.
FAU - Kunkel, George H
AU  - Kunkel GH
AD  - Department of Physiology, School of Medicine, Health Sciences Centre, University 
      of Louisville, A-1215, 500, South Preston Street, Louisville, KY, 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Department of Physiology, School of Medicine, Health Sciences Centre, University 
      of Louisville, A-1215, 500, South Preston Street, Louisville, KY, 40202, USA.
LA  - eng
GR  - HL-74185/National Institutes of Health/
PT  - Journal Article
PT  - Review
DEP - 20170406
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Cytokines)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Chronic Disease
MH  - Cytokines/genetics/*immunology
MH  - Humans
MH  - Hyperhomocysteinemia/genetics/*immunology/pathology
MH  - Toll-Like Receptor 4/genetics/*immunology
MH  - Vascular Remodeling/*immunology
MH  - Vasculitis/genetics/*immunology/pathology
OTO - NOTNLM
OT  - Homocysteine
OT  - Immunity
OT  - Inflammation
OT  - Remodeling
OT  - Toll-like receptor 4
EDAT- 2017/04/08 06:00
MHDA- 2018/07/10 06:00
CRDT- 2017/04/08 06:00
PHST- 2016/12/12 00:00 [received]
PHST- 2017/04/01 00:00 [accepted]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2018/07/10 06:00 [medline]
PHST- 2017/04/08 06:00 [entrez]
AID - 10.1007/s11010-017-3026-9 [pii]
AID - 10.1007/s11010-017-3026-9 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2017 Sep;433(1-2):177-194. doi: 10.1007/s11010-017-3026-9. Epub 
      2017 Apr 6.