PMID- 27158377
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160509
LR  - 20201001
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 8
IP  - 2
DP  - 2016
TI  - Relation between anti-atherosclerotic effects of IRAK4 and modulation of vascular 
      smooth muscle cell phenotype in diabetic rats.
PG  - 899-910
AB  - Deregulation of phenotypic modulation in VSMCs is the initial stage of 
      atherosclerosis, especially in diabetes. Functional deficiency of IRAK4 inhibits 
      the formation of vascular lesions in ApoE-/- mice. Therefore, in this study, we 
      examined the functions of IRAK4 in the regulation of VSMCs differentiation and 
      phenotypic modulation at the levels of transcription and translation in T2D rats. 
      The T2D rat model was generated by feeding a high-fat diet and injecting a low 
      dose of streptozotocin intraperitoneally. VSMCs were isolated from the thoracic 
      aortas of the T2D rats. VSMCs proliferation and migration were measured using 
      water soluble tetrazolium salt-1 assay, 5-ethynyl-29-deoxyuridine staining and 
      migration assay. IRAK4 was knocked down by siRNA and inhibited by an IRAK1/4 
      inhibitor. The mRNAs and proteins of signal molecules and phenotypic markers were 
      detected by qRT-PCR and western blotting. The results demonstrated that LPS 
      significantly increased viability, cell migration rate and amount of DNA in 
      VSMCs. The IRAK4 inhibitor also reduced LPS-mediated protein expression of myosin 
      heavy chain and nuclear factor kappaB p65 subunit and increased smooth muscle 22alpha 
      expression. Moreover, IRAK4 knock-down reduced the LPS-mediated expression of 
      mRNAs for myosin heavy chain, nuclear factor kappaB p65 subunit, and monocyte 
      chemoattractant protein-1 (MCP-1), but increased the mRNA of smooth muscle 22alpha in 
      VSMCs. The activation of IRAK4 phenotypically modulated VSMCs from 
      differentiation to dedifferentiation. Inactivation of IRAK4 exerts a protective 
      effect on VSMCs differentiation and inhibits inflammation. IRAK4 could therefore 
      be a target for interventions to prevent and treat the initial phase of 
      atherosclerosis.
FAU - Cao, Lijuan
AU  - Cao L
AD  - Institute of Cardiovascular Disease Research, Xuzhou Medical College 84 West 
      Huaihai Road, Xuzhou, Jiangsu, Peoples Republic of China.
FAU - Pan, Defeng
AU  - Pan D
AD  - Department of Cardiology, Affiliated Hospital of Xuzhou Medical College 99 West 
      Huaihai Road, Xuzhou 221002, Jiangsu, Peoples Republic of China.
FAU - Li, Dongye
AU  - Li D
AD  - Institute of Cardiovascular Disease Research, Xuzhou Medical College84 West 
      Huaihai Road, Xuzhou, Jiangsu, Peoples Republic of China; Department of 
      Cardiology, Affiliated Hospital of Xuzhou Medical College99 West Huaihai Road, 
      Xuzhou 221002, Jiangsu, Peoples Republic of China.
FAU - Zhang, Yanbin
AU  - Zhang Y
AD  - Department of Cardiology, Affiliated Hospital of Xuzhou Medical College 99 West 
      Huaihai Road, Xuzhou 221002, Jiangsu, Peoples Republic of China.
FAU - Chen, Qiuping
AU  - Chen Q
AD  - Institute of Cardiovascular Disease Research, Xuzhou Medical College 84 West 
      Huaihai Road, Xuzhou, Jiangsu, Peoples Republic of China.
FAU - Xu, Tongda
AU  - Xu T
AD  - Department of Cardiology, Affiliated Hospital of Xuzhou Medical College 99 West 
      Huaihai Road, Xuzhou 221002, Jiangsu, Peoples Republic of China.
FAU - Li, Wenhua
AU  - Li W
AD  - Department of Cardiology, Affiliated Hospital of Xuzhou Medical College 99 West 
      Huaihai Road, Xuzhou 221002, Jiangsu, Peoples Republic of China.
FAU - Wu, Wanling
AU  - Wu W
AD  - Department of Cardiology, Affiliated Hospital of Xuzhou Medical College 99 West 
      Huaihai Road, Xuzhou 221002, Jiangsu, Peoples Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20160215
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC4846934
OTO - NOTNLM
OT  - IRAK4
OT  - MCP-1
OT  - Type 2 diabetes rat model
OT  - Vascular smooth muscle cells
OT  - phenotypic modulation
EDAT- 2016/05/10 06:00
MHDA- 2016/05/10 06:01
PMCR- 2016/02/15
CRDT- 2016/05/10 06:00
PHST- 2015/10/13 00:00 [received]
PHST- 2016/01/06 00:00 [accepted]
PHST- 2016/05/10 06:00 [entrez]
PHST- 2016/05/10 06:00 [pubmed]
PHST- 2016/05/10 06:01 [medline]
PHST- 2016/02/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2016 Feb 15;8(2):899-910. eCollection 2016.