PMID- 18688033
OWN - NLM
STAT- MEDLINE
DCOM- 20080923
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 173
IP  - 3
DP  - 2008 Sep
TI  - Thrombospondin-2 modulates extracellular matrix remodeling during physiological 
      angiogenesis.
PG  - 879-91
LID - 10.2353/ajpath.2008.080128 [doi]
AB  - Thrombospondin 2 (TSP2) can inhibit angiogenesis in vitro by limiting 
      proliferation and inducing apoptosis of endothelial cells (ECs). TSP2 can also 
      modulate the extracellular levels of gelatinases (matrix metalloproteases, MMPs) 
      and potentially influence the remodeling of the extracellular matrix (ECM). Here, 
      we tested the hypothesis that by regulating MMPs, TSP2 could alter EC-ECM 
      interactions. By using a three-dimensional angiogenesis assay, we show that TSP2, 
      but not TSP1, limited angiogenesis by decreasing gelatinolytic activity in situ. 
      Furthermore, TSP2-null fibroblast-derived ECM, which contains irregular collagen 
      fibrils, was more permissive for EC migration. Investigation of the role of TSP2 
      in physiological angiogenesis in vivo, using excision of the left femoral artery 
      in both TSP2-null and wild-type mice, revealed that TSP2-null mice displayed 
      accelerated recovery of blood flow. This increase was attributable, in part, to 
      an enhanced arterial network in TSP2-null muscles of the upper limb. Angiogenesis 
      in the lower limb was also increased and was associated with increased MMP-9 
      deposition and gelatinolytic activity. The observed changes correlated with the 
      temporal expression of TSP2 in the ischemic muscle of wild-type mice. Taken 
      together, our observations implicate the matrix-modulating activity of TSP2 as a 
      mechanism by which physiological angiogenesis is inhibited.
FAU - Krady, Marie M
AU  - Krady MM
AD  - Department of Pathology, Yale University School of Medicine, New Haven, CT 
      06536-9812, USA.
FAU - Zeng, Jianmin
AU  - Zeng J
FAU - Yu, Jun
AU  - Yu J
FAU - MacLauchlan, Susan
AU  - MacLauchlan S
FAU - Skokos, Eleni A
AU  - Skokos EA
FAU - Tian, Weiming
AU  - Tian W
FAU - Bornstein, Paul
AU  - Bornstein P
FAU - Sessa, William C
AU  - Sessa WC
FAU - Kyriakides, Themis R
AU  - Kyriakides TR
LA  - eng
GR  - R01 GM072194/GM/NIGMS NIH HHS/United States
GR  - GM 072194-01/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080807
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Thrombospondins)
RN  - 0 (thrombospondin 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Movement/physiology
MH  - Endothelial Cells/*metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Fibroblasts
MH  - Hindlimb/*blood supply
MH  - Humans
MH  - Immunohistochemistry
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Neovascularization, Physiologic/*physiology
MH  - Regional Blood Flow
MH  - Thrombospondins/*metabolism
PMC - PMC2527070
EDAT- 2008/08/09 09:00
MHDA- 2008/09/24 09:00
PMCR- 2009/03/01
CRDT- 2008/08/09 09:00
PHST- 2008/08/09 09:00 [pubmed]
PHST- 2008/09/24 09:00 [medline]
PHST- 2008/08/09 09:00 [entrez]
PHST- 2009/03/01 00:00 [pmc-release]
AID - S0002-9440(10)61659-8 [pii]
AID - 10.2353/ajpath.2008.080128 [doi]
PST - ppublish
SO  - Am J Pathol. 2008 Sep;173(3):879-91. doi: 10.2353/ajpath.2008.080128. Epub 2008 
      Aug 7.