PMID- 29861433
OWN - NLM
STAT- MEDLINE
DCOM- 20181002
LR  - 20181207
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 23
IP  - 6
DP  - 2018 May 26
TI  - Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats 
      via Inhibiting Inflammatory Response.
LID - 10.3390/molecules23061274 [doi]
LID - 1274
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by increased 
      pulmonary vascular resistance, leading to right ventricular failure and death. 
      Recent studies have suggested that chronic inflammatory processes are involved in 
      the pathogenesis of PAH. Several studies have demonstrated that betaine possesses 
      outstanding anti-inflammatory effects. However, whether betaine exerts protective 
      effects on PAH by inhibiting inflammatory responses in the lungs needs to be 
      explored. To test our hypothesis, we aimed to investigate the effects of betaine 
      on monocrotaline-induced PAH in rats and attempted to further clarify the 
      possible mechanisms. METHODS: PAH was induced by monocrotaline (50 mg/kg) and 
      oral administration of betaine (100, 200, and 400 mg/kg/day). The mean pulmonary 
      arterial pressure, right ventricular systolic pressure, and right ventricle 
      hypertrophy index were used to evaluate the development of PAH. Hematoxylin and 
      eosin staining and Masson staining were performed to measure the extents of 
      vascular remodeling and proliferation in fibrous tissue. Monocyte chemoattractant 
      protein-1 (MCP-1) and endothelin-1 (ET-1) were also detected by 
      immunohistochemical staining. Nuclear factor-kappaB (NF-kappaB), tumor necrosis factor 
      alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were assessed by Western blot. RESULTS: 
      This study showed that betaine improved the abnormalities in right ventricular 
      systolic pressure, mean pulmonary arterial pressure, right ventricle hypertrophy 
      index, and pulmonary arterial remodeling induced by monocrotaline compared with 
      the PAH group. The levels of MCP-1 and ET-1 also decreased. Western blot 
      indicated that the protein expression levels of NF-kappaB, TNF-alpha, and IL-1beta 
      significantly decreased (p < 0.01). CONCLUSION: Our study demonstrated that 
      betaine attenuated PAH through its anti-inflammatory effects. Hence, the present 
      data may offer novel targets and promising pharmacological perspectives for 
      treating monocrotaline-induced PAH.
FAU - Yang, Jia-Mei
AU  - Yang JM
AD  - Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. 
      m15809581390@163.com.
FAU - Zhou, Ru
AU  - Zhou R
AD  - Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. 
      zhou-ru926@163.com.
AD  - Ningxia Hui Medicine Modern Engineering Research Center and Collaborative 
      Innovation Center, Ningxia Medical University, Yinchuan 750004, China. 
      zhou-ru926@163.com.
AD  - Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, 
      Ningxia Medical University, Yinchuan 750004, China. zhou-ru926@163.com.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. 
      18209511903@163.com.
FAU - Tan, Huan-Ran
AU  - Tan HR
AD  - Department of Pharmacology, Peking University, Health Science Center, Beijing 
      100191, China. tanlab@bjmu.edu.cn.
FAU - Yu, Jian-Qiang
AU  - Yu JQ
AD  - Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China. 
      Yujqlab@163.com.
AD  - Ningxia Hui Medicine Modern Engineering Research Center and Collaborative 
      Innovation Center, Ningxia Medical University, Yinchuan 750004, China. 
      Yujqlab@163.com.
LA  - eng
PT  - Journal Article
DEP - 20180526
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Endothelin-1)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 3SCV180C9W (Betaine)
RN  - 73077K8HYV (Monocrotaline)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Betaine/*pharmacology
MH  - Biomarkers
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Endothelin-1/metabolism
MH  - Hemodynamics/drug effects
MH  - Hypertension, Pulmonary/drug therapy/*etiology/metabolism/*physiopathology
MH  - Hypertrophy, Right Ventricular/drug therapy/etiology/pathology
MH  - Immunohistochemistry
MH  - Inflammation Mediators/metabolism
MH  - Male
MH  - Monocrotaline/*adverse effects
MH  - Myocardium/metabolism/pathology
MH  - NF-kappa B/metabolism
MH  - Pulmonary Artery/*drug effects/*physiopathology
MH  - Rats
PMC - PMC6100216
OTO - NOTNLM
OT  - betaine
OT  - inflammatory response
OT  - pulmonary arterial hypertension
COIS- The authors declare no conflict of interest associated with this work.
EDAT- 2018/06/05 06:00
MHDA- 2018/10/03 06:00
PMCR- 2018/05/26
CRDT- 2018/06/05 06:00
PHST- 2018/04/11 00:00 [received]
PHST- 2018/05/16 00:00 [revised]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/06/05 06:00 [entrez]
PHST- 2018/06/05 06:00 [pubmed]
PHST- 2018/10/03 06:00 [medline]
PHST- 2018/05/26 00:00 [pmc-release]
AID - molecules23061274 [pii]
AID - molecules-23-01274 [pii]
AID - 10.3390/molecules23061274 [doi]
PST - epublish
SO  - Molecules. 2018 May 26;23(6):1274. doi: 10.3390/molecules23061274.