Journal
PATHOPHYSIOLOGY
Volume 29, Issue 3, Pages 570-582Publisher
MDPI
DOI: 10.3390/pathophysiology29030044
Keywords
biomarkers; multiple sclerosis; microparticles; brain endothelial cells; MS serum samples
Categories
Funding
- Center for Redox Biology and Cardiovascular Disease Center of Biomedical Research Excellence - National Institute of General Medical Sciences IDeA program of the National Institutes of Health [P20GM121307]
- IDeA Center of Biomedical Research Excellence grant [P20GM103424]
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Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. Finding specific serum biomarkers for early-stage MS can facilitate more effective treatment. This study found increased levels of CSE and decreased levels of CBS and MST in the serum samples of MS patients, indicating an association with vascular inflammation.
Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine ?-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-a (TNF-a) and interferon-? (IFN-?). CSE was increased in MPs and cells by exposure to TNF-a/IFN-?; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, liquid biopsy can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.
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