Association of matrix metalloproteinases with MRI indices of brain ischemia and aging

被引:25
|
作者
Romero, Jose Rafael [1 ]
Vasan, Ramachandran S. [2 ,3 ,6 ]
Beiser, Alexa S. [1 ,4 ,6 ]
Au, Rhoda [1 ,6 ]
Benjamin, Emelia J. [2 ,3 ,6 ]
DeCarli, Charles [5 ]
Wolf, Philip A. [1 ,6 ]
Seshadri, Sudha [1 ,6 ]
机构
[1] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA
[4] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA
[5] Univ Calif Davis, Dept Neurol, Framingham, MA USA
[6] NHLBIs Framingham Heart Study, Framingham, MA USA
关键词
MMPs; Brain MRI; Framingham; Brain aging; CARDIOVASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; TISSUE INHIBITOR; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; VASCULAR DEMENTIA; CEREBRAL-ISCHEMIA; CELL-DEATH; MATRIX-METALLOPROTEINASE-9; STROKE;
D O I
10.1016/j.neurobiolaging.2008.11.004
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Magnetic resonance imaging (MRI) findings of large white matter hyperintensities (LWMH), decreased brain volume and silent cerebral infarcts (SCI) are subclinical indices of brain ischemia and aging. Although the pathophysiology of these findings remains uncertain, extracellular matrix (ECM) remodeling, a process regulated by matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), may be implicated. We evaluated the cross-sectional relations of circulating MMP-9 and TIMP-1 to these MRI indices in 583 stroke and dementia-free, Framingham Offspring participants (mean age 57 years, 58% women). Using multivariable regression MMP-9 (detectable versus non-detectable) and TIMP-1 (modeled as sex-specific quartiles) were related to LWMH (>1 S.D. above age-specific mean; yes/no), SCI (yes/no) and total brain volume (ratio of parenchymal to intracranial volume, TCBVr). Mean TCBVr was 0.78 (S.D. 0.03), 13% of subjects had LWMH and 12% had SCI. Detectable MMP-9 was associated with higher prevalence of LWMH (OR 2.09, 95%confidence interval (Cl) 1.00-4.37), but not with TCBVr. TIMP-1 was associated with a high prevalence of LWMH (OR for Q4 versus Q1-3: 1.83, 95%CI 1.06-3.18) and with lower mean TCBVr (Q4 associated with 0.17 S.D. units lower value relative to Q1-3; p = 0.04). Neither biomarker was associated with SCI. Our findings are preliminary but if confirmed in further studies, suggest a pathophysiological role for the MMP/TIMP pathway in processes of brain ischemia and aging. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:2128 / 2135
页数:8
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