PMID- 34368236
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210810
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - LncRNA ENSMUST00000155383 is Involved in the Improvement of DPP-4 Inhibitor 
      MK-626 on Vascular Endothelial Function by Modulating Cacna1c-Mediated Ca(2+) 
      Influx in Hypertensive Mice.
PG  - 724225
LID - 10.3389/fmolb.2021.724225 [doi]
LID - 724225
AB  - Objective: This study investigated the protective effects of dipeptidyl 
      peptidase-4 inhibitor MK-626 on vascular endothelial function by regulating 
      lncRNAs in hypertensive vasculature. Methods: Angiotensin Ⅱ (Ang Ⅱ)-loaded 
      osmotic pumps were implanted in mice with or without MK-626 administration. GLP-1 
      levels in plasma were measured by ELISA. Aortic rings were suspended in myograph 
      for tension measurement. Microarray was performed to analyze lncRNA and mRNA 
      expression profiles. Protein expression and phosphorylation were examined by 
      Western blot. The differentially expressed (DE)-genes were validated by qRT-PCR. 
      The intracellular Ca(2+) concentration was detected by laser confocal system. 
      Results: MK-626 elevated plasma GLP-1 level, increased eNOS phosphorylation, 
      improved endothelium-dependent relaxations, and reduced systolic blood pressure 
      in Ang Ⅱ-induced hypertensive mice. Microarray revealed the dysregulations of 723 
      lncRNAs and 742 mRNAs were reversed by MK-626 in hypertensive mouse aortae. 
      qRT-PCR validation showed that 13 DE-lncRNAs and eight dysregulated mRNAs in both 
      hypertensive mouse aortae and mouse aortic endothelial cells (MAECs) were rescued 
      by MK-626. Among them, four mRNAs (Cacna1C, Itgav, Itga8, and Npnt) were 
      co-expressed with lncRNA ENSMUST00000155383. Cacna1C protein expression was 
      reduced in the ECs but was elevated in smooth muscle cells from Ang Ⅱ-infused 
      mice, which were both reversed by MK-626. Knockdown of lncRNA ENSMUST00000155383 
      suppressed the increased Cacna1c protein and mRNA expression, elevated Ca(2+) 
      level, and enhanced eNOS phosphorylation induced by MK-626 in the hypertensive 
      mouse ECs. Conclusion: The dysregulations of lncRNA ENSMUST00000155383-associated 
      genes might play crucial roles in hypertension-induced endothelial dysfunction 
      through affecting calcium pathway. MK-626 might ameliorate endothelial 
      dysfunction by upregulating lncRNA ENSMUST00000155383, enhancing Ca(2+) 
      concentration, and subsequently restoring eNOS activity in hypertension.
CI  - Copyright (c) 2021 Zhang, Tan, Zong, Li, Zhang, Liu, Wang, Han and Liu.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
FAU - Tan, Na
AU  - Tan N
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
FAU - Zong, Yi
AU  - Zong Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
FAU - Li, Li
AU  - Li L
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
AD  - Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, 
      Beijing, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
AD  - Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, 
      Beijing, China.
FAU - Liu, Jian
AU  - Liu J
AD  - Department of Integration of Chinese and Western Medicine, School of Basic 
      Medical Sciences, Peking University, Beijing, China.
FAU - Wang, Xiaorui
AU  - Wang X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
FAU - Han, Wenwen
AU  - Han W
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
FAU - Liu, Limei
AU  - Liu L
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University, Beijing, China.
AD  - Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, 
      Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20210723
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8343177
OTO - NOTNLM
OT  - calcium
OT  - endothelial function
OT  - glucagon-like peptide-1
OT  - hypertension
OT  - long noncoding RNA
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/10 06:00
MHDA- 2021/08/10 06:01
PMCR- 2021/01/01
CRDT- 2021/08/09 06:42
PHST- 2021/06/12 00:00 [received]
PHST- 2021/07/14 00:00 [accepted]
PHST- 2021/08/09 06:42 [entrez]
PHST- 2021/08/10 06:00 [pubmed]
PHST- 2021/08/10 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 724225 [pii]
AID - 10.3389/fmolb.2021.724225 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Jul 23;8:724225. doi: 10.3389/fmolb.2021.724225. 
      eCollection 2021.