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https://doi.org/10.1177/0271678X221146401
Title: | Chronic cerebral hypoperfusion alters the CypA-EMMPRIN-gelatinase pathway: Implications for vascular dementia | Authors: | Chai, Yuek Ling Rajeev, Vismitha Poh, Luting Selvaraji, Sharmelee Hilal, Saima Chen, Christopher P Jo, Dong-Gyu Koo, Edward H Arumugam, Thiruma Lai, Mitchell KP |
Keywords: | Science & Technology Life Sciences & Biomedicine Endocrinology & Metabolism Hematology Neurosciences Neurosciences & Neurology Cerebrovascular disease chronic cerebral hypoperfusion cyclophilin A gelatinase vascular dementia WHITE-MATTER LESIONS MATRIX-METALLOPROTEINASE EXPRESSION BRAIN-BARRIER DISRUPTION SMALL VESSEL DISEASE SUBARACHNOID HEMORRHAGE EXTRACELLULAR-MATRIX GLIAL ACTIVATION BLOOD MMP-9 PATHOPHYSIOLOGY |
Issue Date: | May-2023 | Publisher: | SAGE PUBLICATIONS INC | Citation: | Chai, Yuek Ling, Rajeev, Vismitha, Poh, Luting, Selvaraji, Sharmelee, Hilal, Saima, Chen, Christopher P, Jo, Dong-Gyu, Koo, Edward H, Arumugam, Thiruma, Lai, Mitchell KP (2023-05). Chronic cerebral hypoperfusion alters the CypA-EMMPRIN-gelatinase pathway: Implications for vascular dementia. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 43 (5) : 722-735. ScholarBank@NUS Repository. https://doi.org/10.1177/0271678X221146401 | Abstract: | Chronic cerebral hypoperfusion (CCH) is postulated to underlie multiple pathophysiological processes in vascular dementia (VaD), including extracellular matrix dysfunction. While several extracellular matrix proteins, namely cyclophilin A (CypA), extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases (matrix metalloproteinases, MMP-2 and -9) have been investigated in acute stroke, their involvement in CCH and VaD remains unclear. In this study, CypA-EMMPRIN-gelatinase proteins were analysed in a clinical cohort of 36 aged, cognitively unimpaired subjects and 48 VaD patients, as well as in a bilateral carotid artery stenosis mouse model of CCH. Lower CypA and higher EMMPRIN levels were found in both VaD serum and CCH mouse brain. Furthermore, gelatinases were differentially altered in CCH mice and VaD patients, with significant MMP-2 increase in CCH brain and serum, whilst serum MMP-9 was elevated in VaD but reduced in CCH, suggesting complex CypA-EMMPRIN-gelatinase regulatory mechanisms. Interestingly, subjects with cortical infarcts had higher serum MMP-2, while white matter hyperintensities, cortical infarcts and lacunes were associated with higher serum MMP-9. Taken together, our data indicate that perturbations of CypA-EMMPRIN signalling may be associated with gelatinase-mediated vascular sequelae, highlighting the potential utility of the CypA-EMMPRIN-gelatinase pathway as clinical biomarkers and therapeutic targets in VaD. | Source Title: | JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | URI: | https://scholarbank.nus.edu.sg/handle/10635/241008 | ISSN: | 0271-678X 1559-7016 |
DOI: | 10.1177/0271678X221146401 |
Appears in Collections: | Staff Publications Elements |
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