Matrix metalloproteinases during and outside of migraine attacks without aura

Abstract

To test the hypothesis that permeability of the blood-brain barrier (BBB) is altered during migraine attack due to enhanced activation of matrix metalloproteinases (MMPs), we investigated MMP-3, MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 in the external jugular vein during and outside of migraine attacks in 21 patients with migraine without aura. In addition, we measured plasma levels of several other proteins including MMP-7, -8, -10 and TIMP-2. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study plasma concentration of MMPs. There was no difference in MMP-9 and TIMP-1 levels between ictal and interictal periods. We found significantly decreased plasma levels of MMP-3 in the external jugular (P = 0.002) and cubital (P = 0.008) vein during attacks compared with outside of attacks. We found no correlation of ictal or interictal MMP-3, MMP-9 and TIMP-1 to migraine duration and frequency analysed in 21 patients (P > 0.05). There was no difference between ictal and interictal plasma levels of MMP-7, -8, -10 and TIMP-2 (P > 0.05). Our data suggest that plasma MMP-9 cannot be used as a biomarker of BBB disruption in migraine without aura. Decreased MMP-3 levels are an interesting and unexpected finding warranting further investigation.

The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia

“…We sorted genes that were increased over 2-fold in the MCAO group compared with normal group, then screened for genes that were down-regulated more than 2-fold in the si-ASK1 group compared with the MCAO group. Several genes were selected, including matrix metallopeptidase 3 (MMP3) (Ashina et al, 2010), integrin alpha 8 (Itga8) (Cucullo et al, 2011;Osada et al, 2011), cadherin 1 (Cdh1) (Zechariah et al, 2013), gap junction protein beta 1 (Gjb3) (Song et al, 2007), Selectin (Sele) (Jin et al, 2010), intercellular adhesion molecule 1 (Icam1) (An and Xue, 2009), aquaporin 8 (Aqp8) (Richard et al, 2003), aquaporin 12 (Aqp12) (Calvanese et al, 2013) related with vascular permeability. Also, vascular endothelial growth factor A (Vegfa) (Gong et al, 2014;Poittevin et al, 2014), and vascular endothelial growth factor C (Vegfc) (Foster et al, 2008;Xu et al, 2013) which are related with vascular permeability were down-regulated in the si-ASK1 group compared with the MCAO group slightly.…”

The impact of triptan and doxycycline on neuroinflammatory biomarkers in acute migraine: study protocol of a randomized controlled trial

“…According to the literature (19)(20)(21)(22), the 95% confidence interval for the difference in means of MMP-9 between the migraine group and the control group will be approximately 50 ± 30 ng/mL. It is expected that the confidence intervals for the inter-ictal and post-treatment differences in the treated group will be considerably narrower due to the elimination of patient-to-patient variation when analyzing our primary endpoint.…”

“…An alteration of MMP expression may lead to the breakdown of the BBB, demyelination, cytokine production and an inflammatory response, deposition of amyloid proteins, and tumor invasion and metastasis [14][15][16][17][18]. In migraine, post-headache levels of MMP-9 were significantly higher than controls [19][20][21][22]. MMP-9 potentiates chemokines for leukocyteendothelial cell interaction leading to an inflammation cascade at the brain vasculature.…”

Specific matrix metalloproteinase 9 (MMP-9) haplotype affect the circulating MMP-9 levels in women with migraine

“…Interestingly, we found that MA patients, but not MWA patients, had lower MMP-9 and higher TIMP-1 concentrations than healthy controls, thus suggesting that higher TIMP-1 levels could be associated with MMP-9 plasma reduction in MA patients, although we have not determined the mechanisms possibly involved in these differences. Another study showed that MMP-9 levels were not correlated with the frequency or duration of migraine attacks (Ashina et al, 2010). It is highly probable that some differences between studies may explain differences in MMP-9 levels.…”