Association of Brain-Gut Peptides with Inflammatory Cytokines in Moyamoya Disease

Abstract

Systemic inflammation has been shown to play a pivotal role in the pathogenesis of moyamoya disease (MMD). Brain-gut peptides exhibit regulatory effects in the secretion of proinflammatory cytokines. To investigate the association between brain-gut peptides and inflammation in the occurrence of MMD, 41 patients with MMD, as well as 74 age- and sex-matched healthy individuals were enrolled. The levels of four brain-gut peptides (vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), somatostatin (SST), substance P (SP)) and three proinflammatory cytokines (interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-12) in the serum and cerebrospinal fluid (CSF) were measured using the enzyme-linked immunosorbent assay. The associations between brain-gut peptides and proinflammatory cytokines were estimated according to the multiple linear regression and correlation analyses. MMD patients exhibited significantly lower levels of VIP, CCK, and SST and higher levels of IL-1β, TNF-α, and IL-12 in the serum compared with healthy controls. Multiple logistic regression analysis showed that decreased VIP, CCK, and SST levels were independent predictors of the occurrence of MMD. Negative correlations were observed between the VIP and proinflammatory cytokines, including IL-1β, TNF-α, and IL-12 (serum vs. CSF). Significant negative correlations were also found between CCK and IL-1β, as well as IL-12 (serum vs. CSF). SST was negatively correlated with IL-1β and TNF-α in the serum and IL-1β only in the CSF. In addition, the levels of VIP, CCK, SST, and proinflammatory cytokines IL-1β and TNF-α in the serum were correlated with those measured in the CSF. Collectively, lower levels of VIP, CCK, and SST may be associated with the pathogenesis of MMD and act as clinically useful biomarkers along with the levels of proinflammatory cytokines.

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow‑derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

“…Moyamoya disease (MMD) was first defined by Suzuki and Takaku in 1999( 1 ) and presents as the presence of an abnormal vascular network at the base of the brain. MMD is characterized by progressive stenosis and even occlusion of the terminal portion of the bilateral internal carotid and intracerebral arteries ( 2 ). The most common symptoms of MMD include headache, ischemia and hemorrhage ( 3 ).…”

Association of circulating branched-chain amino acids with risk of moyamoya disease

“…Recent studies have found that the expression levels of periphery inflammatory factors in MMD were higher than those in HCs, including TNF-α, IL1-β, IL-6, etc. (28,29). The microenvironment formed by abnormally secreted inflammatory factors may promote the proliferation and angiogenesis of cells in affected vessels (30).…”

Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio in Patients With Newly Diagnosed Moyamoya Disease: A Cross-Sectional Study

“…Some researches manifest that MMD could be the result of vascular immune injury and inflammation response ( 2 , 30 ). Recent studies of our team have found that the upregulated expressions of various plasma inflammatory factors, such as IL-1β, IL-12, and TNF-α, in patients with MMD suggested that inflammation might regulate the process of MMD ( 31 ). Inflammatory response ultimately leads to the hyperplasia of intimal vascular smooth muscle cells and neovascularization by proliferation of endothelial cells, that motivates lumen stenosis and collateral formation ( 32 ).…”