title: Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice†.
abstract: OBJECTIVE
  About one-third of American adults and 20% of teenagers are obese. Obesity and its associated metabolic disturbances including hyperlipidaemia are risk factors for cardiovascular diseases including stroke. They can worsen neurological outcome after stroke. We determined whether obesity and hyperlipidaemia could induce cerebral vascular remodelling via matrix metalloproteases (MMP) and whether this remodelling affected neurological outcome after brain ischaemia.
  
  
  RESULTS
  Six-week-old male CD1, C57BL/6J, and MMP-9(-/-) mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks. They were subjected to vascular casting or a 90 min middle cerebral arterial occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral vascular tortuosity index and decreased inner diameters of the middle cerebral arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex. After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe brain oedema and blood-brain barrier damage, higher haemorrhagic transformation rate, greater haemorrhagic volume, and worse neurological function. HFD increased MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD increased the body weights, blood glucose, and lipid levels in the MMP-9(-/-) mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular remodelling and worsening of neurological outcome did not occur in these mice.
  
  
  CONCLUSIONS
  HFD induces cerebral vascular remodelling and worsens neurological outcome after transient focal brain ischaemia. MMP-9 activation plays a critical role in these HFD effects.
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA.
authors.forename: Chenzhuo
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, People's Republic of China zz3c@virginia.edu mzkxlz@126.com.
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA zz3c@virginia.edu mzkxlz@126.com.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D001930:Brain Injuries / Q000201:enzymology*; D002545:Brain Ischemia / Q000201:enzymology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D066253:Vascular Remodeling / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Cerebral vascular remodelling; High fat diet; Ischemic stroke; Matrix metalloprotease; Mouse