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

José Rafael Romero, Ramachandran S. Vasan, Alexa S. Beiser, Rhoda Au, Emelia J. Benjamin, Charles DeCarli, Philip A. Wolf, Sudha Seshadri

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 (CI) 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.

Original languageEnglish (US)
Pages (from-to)2128-2135
Number of pages8
JournalNeurobiology of Aging
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Brain Ischemia
Matrix Metalloproteinases
Magnetic Resonance Imaging
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 9
Confidence Intervals
Matrix Metalloproteinase Inhibitors
Brain
Extracellular Matrix
Dementia
Biomarkers
Stroke
White Matter

Keywords

  • Brain aging
  • Brain MRI
  • Framingham
  • MMPs

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Association of matrix metalloproteinases with MRI indices of brain ischemia and aging. / Romero, José Rafael; Vasan, Ramachandran S.; Beiser, Alexa S.; Au, Rhoda; Benjamin, Emelia J.; DeCarli, Charles; Wolf, Philip A.; Seshadri, Sudha.

In: Neurobiology of Aging, Vol. 31, No. 12, 01.12.2010, p. 2128-2135.

Research output: Contribution to journalArticle

Romero, JR, Vasan, RS, Beiser, AS, Au, R, Benjamin, EJ, DeCarli, C, Wolf, PA & Seshadri, S 2010, 'Association of matrix metalloproteinases with MRI indices of brain ischemia and aging', Neurobiology of Aging, vol. 31, no. 12, pp. 2128-2135. https://doi.org/10.1016/j.neurobiolaging.2008.11.004
Romero, José Rafael ; Vasan, Ramachandran S. ; Beiser, Alexa S. ; Au, Rhoda ; Benjamin, Emelia J. ; DeCarli, Charles ; Wolf, Philip A. ; Seshadri, Sudha. / Association of matrix metalloproteinases with MRI indices of brain ischemia and aging. In: Neurobiology of Aging. 2010 ; Vol. 31, No. 12. pp. 2128-2135.
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abstract = "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 (CI) 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.",
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