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.
Highlights
Moyamoya disease (MMD) is characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches, leading to ischemic or hemorrhagic symptoms [1]
We identified 41 patients as incident cases and matched them with 74 healthy controls
We found that the levels of vasoactive intestinal polypeptide (VIP), CCK, and SST in the serum were significantly decreased in patients with MMD compared with healthy controls
Summary
Moyamoya disease (MMD) is characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches, leading to ischemic or hemorrhagic symptoms [1]. It is a rare disease, more frequently occurring in Asian countries. MMD has been extensively studied over the past years, and certain progress has been achieved in understanding the etiology and pathogenesis of the disease [3,4,5]. It may be related to smooth muscle cell mobilization, migration, and proliferation, which contribute to the development of arterial occlusive lesions [8]. Study in vitro demonstrated the activation and injury of endothelial cells induced by tumor necrosis factor-α (TNF-α) and other proinflammatory cytokines may directly or indirectly play
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