Korean J Physiol Pharmacol.  2014 Apr;18(2):177-182. 10.4196/kjpp.2014.18.2.177.

Expression Profile of Neuro-Endocrine-Immune Network in Rats with Vascular Endothelial Dysfunction

• Li L
• Jia Z
• Xu L
• Wu Y
• Zheng Q

• KMID: 2285508
• DOI: http://doi.org/10.4196/kjpp.2014.18.2.177

Abstract

This study was to determine the correlation between endothelial function and neuro-endocrine-immune (NEI) network through observing the changes of NEI network under the different endothelial dysfunction models. Three endothelial dysfunction models were established in male Wistar rats after exposure to homocysteine (Hcy), high fat diet (HFD) and Hcy+HFD. The results showed that there was endothelial dysfunction in all three models with varying degrees. However, the expression of NEI network was totally different. Interestingly, treatment with simvastatin was able to improve vascular endothelial function and restored the imbalance of the NEI network, observed in the Hcy+HFD group. The results indicated that NEI network may have a strong association with endothelial function, and this relationship can be used to distinguish different risk factors and evaluate drug effects.

Keyword

Endocrine system; Immune system; Nervous system; Vascular endothelial dysfunction

MeSH Terms

Animals
Diet, High-Fat
Endocrine System
Homocysteine
Humans
Immune System
Male
Nervous System
Rats*
Rats, Wistar
Risk Factors
Simvastatin
Homocysteine
Simvastatin

Figure

• 

  Fig. 1 Scatter plot of the ratio of each NEI network index of the test group relative to that of the related control group. Error bars represent the 95% confidence interval of the ratio value. Squares, triangles and circles in the figure indicate that the 95% confidence interval of the ratio value is less than 1, covers 1 or is higher than 1, respectively. The 95% confidence interval of the ratio value was estimated by a 1000 times repeated bootstrapping method.

• 

  Fig. 2 PCA scores (A) and loading plots (B) derived from the scores of separate principle component analyses of the Hcy-, HFD- and Hcy+HFD groups. PCA score plots illustrate that the Hcy-, HFD- and Hcy+HFD groups are well separated from the control, suggesting that the NEI network has been affected due to the different treatments. The major markers responsible for class separation are revealed by the PCA loading plots, which represent the importance to the inter-group differences within the discrimination model. The established PCA model was then used to predict the scores of PCs in the Hcy+HFD+Sim group (C), providing a visual picture of the recovery of the NEI network after treatment with simvasatin. The heat map (D) shows the changes in the NEI network of control group, compared with the Hcy-, HFD- and Hcy+HFD groups, or the Hcy+HFD+Sim group compared with Hcy+HFD group. Shades of red and blue represent fold increase and decrease of the different indices in the indicated groups.

• 

  Fig. 3 The key indices selected from PCA model exemplified a clear distinction among the groups (Mean±SD). Significant difference between each model group (n=10) and the control group (n=10) is based on a two-tailed Dunnett's t-test (*p<0.05, **p<0.01), and significant difference between the Hcy+HFD group (n=10) and the simvastatin group (n=10) is based on a two-tailed student's t-test (Δp<0.05, ΔΔp<0.01).

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