Haeme oxygenase promotes progenitor cell mobilization, neovascularization, and functional recovery after critical hindlimb ischaemia in mice.

Abstract:

AIMS:Neovascularization is an important element of long-term functional recovery during chronic ischaemia. We postulated that haeme oxygenase (HO) is required for progenitor cell recruitment, neovascularization, and blood flow recovery after critical hindlimb ischaemia (HLI). METHODS AND RESULTS:The femoral artery was ligated in FVB/N mice proximal to its superficial and deep branches. Blood flow in the ischaemic hindlimb was determined by laser Doppler perfusion imaging. Capillary density was measured by isolectin staining, and mobilization of Sca-1(+)/Kdr(+) progenitor cells by FACS analysis. Progenitor cell recruitment to the ischaemic hindlimb was assessed after Tie2-lacZ transgenic bone marrow transplantation. Blood flow recovery after femoral artery ligation was significantly blunted in mice treated with the HO inhibitor tin protoporphyrin-IX (25 mg/kg i.p., every other day). HO-inhibited mice developed more pronounced limb necrosis, associated with impaired hindlimb motor function. Capillary density in the ischaemic hindlimb and mobilization of Sca-1(+)/Kdr(+) progenitor cells were significantly reduced after HO inhibition. After transplantation of Tie2-lacZ transgenic bone marrow cells into lethally irradiated wild-type mice, fewer LacZ(+) cells were detected in the ischaemic hindlimb muscle of HO-inhibited mice. Mechanistically, HO inhibition prevented the establishment of a stromal cell-derived factor-1 gradient for progenitor cell mobilization between the ischaemic hindlimb and bone marrow. CONCLUSION:HOs are required for progenitor cell recruitment, neovascularization, and functional recovery after HLI.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Tongers J,Knapp JM,Korf M,Kempf T,Limbourg A,Limbourg FP,Li Z,Fraccarollo D,Bauersachs J,Han X,Drexler H,Fiedler B,Wollert KC

doi

10.1093/cvr/cvm107

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

294-300

issue

2

eissn

0008-6363

issn

1755-3245

pii

cvm107

journal_volume

78

pub_type

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