PMID- 33052879
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230202
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 19
DP  - 2020 Oct 14
TI  - Apremilast ameliorates ox-LDL-induced endothelial dysfunction mediated by KLF6.
PG  - 19012-19021
LID - 10.18632/aging.103665 [doi]
AB  - Apremilast is a phosphodiesterase 4 (PDE4) inhibitor used in the treatment of 
      psoriasis and several other inflammatory diseases. Interest has been expressed in 
      seeking out therapies that address both psoriasis and atherosclerosis. In the 
      present study, we explored the effects of apremilast in human aortic endothelial 
      cells (HAECs) exposed to oxidized low-density lipoprotein (ox-LDL) to simulate 
      the atherosclerotic microenvironment in vitro. Our findings indicate that 
      apremilast may reduce the expression of lectin-like 
      oxidized-low-density-lipoprotein receptor-1 (LOX-1), the main ox-LDL scavenging 
      receptor. Apremilast also inhibited the expression of tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8), which are deeply 
      involved in the chronic inflammatory response associated with atherosclerosis. 
      Interestingly, we found that apremilast inhibited the attachment of U937 
      monocytes to HAECs by reducing the expression of the chemokine monocyte 
      chemotactic protein 1 (MCP-1) and the cellular adhesion molecule vascular cell 
      adhesion molecule-1 (VCAM-1). This effect was found to be mediated through the 
      rescue of Kruppel like factor 6 (KLF6) expression, which was reduced in response 
      to ox-LDL via increased phosphorylation of c-Jun N-terminal kinase (JNK). These 
      findings suggest a potential role for apremilast in the treatment of 
      atherosclerosis.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Cardiology, The Second Medical Center, National Clinical Research 
      Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Yang, Guang
AU  - Yang G
AD  - Department of Nephrology, The Second Medical Center, National Clinical Research 
      Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Zhang, Qian
AU  - Zhang Q
AD  - Department of Endocrinology, The Seventh Medical Center, Chinese PLA General 
      Hospital, Beijing 100700, China.
FAU - Liang, Xiao
AU  - Liang X
AD  - Department of Cardiology, The Second Medical Center, National Clinical Research 
      Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Nephrology, The Second Medical Center, National Clinical Research 
      Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Gao, Meng
AU  - Gao M
AD  - Department of Cardiology, The Second Medical Center, National Clinical Research 
      Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Guo, Yutao
AU  - Guo Y
AD  - Department of Cardiology, The First Medical Center, Chinese PLA General Hospital, 
      Beijing 100853, China.
FAU - Chen, Li
AU  - Chen L
AD  - Department of General Practice, The First Medical Center, Chinese PLA General 
      Hospital, Beijing 100853, China.
LA  - eng
PT  - Journal Article
DEP - 20201014
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
SB  - IM
PMC - PMC7732304
OTO - NOTNLM
OT  - KLF6
OT  - apremilast
OT  - atherosclerosis
OT  - endothelial dysfunction
OT  - ox-LDL
COIS- CONFLICTS OF INTEREST: These authors declare no conflicts of interest.
EDAT- 2020/10/15 06:00
MHDA- 2020/10/15 06:01
PMCR- 2020/10/15
CRDT- 2020/10/14 17:59
PHST- 2020/05/07 00:00 [received]
PHST- 2020/06/22 00:00 [accepted]
PHST- 2020/10/15 06:00 [pubmed]
PHST- 2020/10/15 06:01 [medline]
PHST- 2020/10/14 17:59 [entrez]
PHST- 2020/10/15 00:00 [pmc-release]
AID - 103665 [pii]
AID - 10.18632/aging.103665 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 Oct 14;12(19):19012-19021. doi: 10.18632/aging.103665. 
      Epub 2020 Oct 14.