Premium
Disruption of endothelial cell/pericyte adhesion by PAI‐1 in ischemic limb of diabetic mouse
Author(s) -
Wu Jianbo,
Strawn Tammy L,
William Fay P
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1057.18
Subject(s) - medicine , pericyte , endocrinology , diabetes mellitus , streptozotocin , microangiopathy , endothelial dysfunction , endothelial stem cell , endothelium , chemistry , in vitro , biochemistry
Background Disruption of pericytes and acellular capillariesare increased in the feet of human diabetic patients. Selectiveloss of adhesion of pericytes to endothelial cells is known toearly event in diabetic microangiopathy. In diabetes, increased levels of PAI‐1 are strongly associated with endothelial dysfunction and progression. Based on these findings, we investigated whether PAI‐1 plays a role in modulating endothelial/pericyte adhesion inischemic hindlimbs of diabetic mice. Methods Type I diabetes was induced by intraperitoneal administrationof streptozocin in both PAI‐1 deficient mice (PAI‐1 −/− ) and WT mice. Ligation of femoral arterywas conducted to develop hindlimb ischemia. Plasma was collected for measurement of PAI‐1 and advanced glycated end products (AGE) levels by ELISA. Ischemic gastroceminus muscles were isolated. Adhesion ofpericytes to endothelial cells was assessed by scanning confocal and electron microscopy. Results Plasma total and active PAI‐1 levels were significantly increased in WT mice with STZ‐induced diabetes. PAI‐1 −/− ‐STZ was found to suppress plasma AGE level compared to WT‐STZ mice (basal level: 4.74 ± 1.19 Vs. 4.28 ± 1.03, n=8; STZ status: 5.54 ± 0.28 Vs. 9.75 ± 1.73, n=8, p< 0.05). Attachment between endothelial cell andpericyte from schemic gastroceminus muscles in PAI‐1 −/− ‐STZ was markedly increased compared with that in WT‐STZ mice. Conclusions Increased PAI‐1 levels disrupt endothelial cell/pericyte adhesionin ischemic limb of the diabetic mouse. These results identify an important role for PAI‐1 in diabetic microangiopathy.