期刊
GEROSCIENCE
卷 43, 期 5, 页码 2611-2619出版社
SPRINGER
DOI: 10.1007/s11357-021-00402-5
关键词
Microbleed; Artery; Arteriole; Cerebral microhemorrhage; Stroke; Oxidative stress; Aging
资金
- American Heart Association
- Oklahoma Center for the Advancement of Science and Technology
- National Institute on Aging [R01-AG055395, R01-AG047879, R01-AG038747, R01-AG072295, K01AG073614]
- National Institute of Neurological Disorders and Stroke (NINDS) [R01-NS100782]
- National Cancer Institute (NCI) [1R01CA255840]
- Oklahoma Shared Clinical and Translational Resources (OSCTR) program - National Institute of General Medical Sciences [U54GM104938]
- Presbyterian Health Foundation
- NKFIH
- NIA [T32AG052363]
- Oklahoma Nathan Shock Center [P30AG050911]
- Cellular and Molecular GeroScience CoBRE [1P20GM125528, 5337]
Clinical and experimental studies have shown that hypertension leads to intracerebral hemorrhages, with aging exacerbating the activation of matrix metalloproteinases (MMPs) mediated by oxidative stress, but the activation of MMP-9 does not play a role in the age-related exacerbation of hypertension-induced ICH.
Clinical and experimental studies show that hypertension induces intracerebral hemorrhages (ICH), including cerebral microhemorrhages in the aged brain, which contribute to the pathogenesis of vascular cognitive impairment (VCI). Previous studies showed that aging increased oxidative stress-mediated activation of matrix metalloproteinases (MMPs) that importantly contributes to the pathogenesis of ICHs. In particular, oxidative stress has been implicated in activation of MMP-9, which is known to be involved in the degradation of the extracellular matrix and cleavage of collagen IV, a key constituent of the basal membrane of cerebral vessels. To determine the role of MMP-9 activation in the genesis of ICHs, we induced hypertension in 20-month-old MMP-9 null and age-matched control mice by angiotensin II and L-NAME treatment. Contrary to our hypothesis, MMP-9 deficiency did not delay the onset or incidence of neurological consequences of hypertension-induced ICHs. Our results indicate that MMP-9 activation does not play a role in the age-related exacerbation of hypertension-induced ICH.
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