Differential gene and protein expression in abluminal sprouting and intraluminal splitting forms of angiogenesis.
In adult skeletal muscle, abluminal sprouting or longitudinal splitting of capillaries can be initiated separately by muscle overload and elevated microcirculation shear stress respectively. In the present study, gene and protein expression patterns associated with the different forms of angiogenesis were examined using a targeted gene array (Superarray), validated by quantitative RT (reverse transcription)-PCR and immunoblots. Sprouting angiogenesis induced large changes in expression levels in genes associated with extracellular matrix remodelling, such as MMP-2 (matrix metalloproteinase-2), TIMP (tissue inhibitor of metalloproteinases), SPARC (secreted protein, acidic and rich in cysteine) and thrombospondin. Changes in neuropilin, midkine and restin levels, which may underpin changes in endothelial morphology, were seen during splitting angiogenesis. Up-regulation of VEGF (vascular endothelial growth factor), Flk-1, angiopoietin-2 and PECAM-1 (platelet/endothelial cell adhesion molecule-1) was seen in both forms of angiogenesis, representing a common angiogenic response of endothelial cells. In conclusion, the present study demonstrates that general angiogenic signals from growth factors can be influenced by the local microenvironment resulting in differing forms of capillary growth to produce a co-ordinated expansion of the vascular bed.
Williams
James L
JL
Angiogenesis Research Group, Division of Cardiovascular Sciences, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK.
Weichert
Alexander
A
Zakrzewicz
Andreas
A
Da Silva-Azevedo
Luis
L
Pries
Axel R
AR
Baum
Oliver
O
Egginton
Stuart
S
D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002196:Capillaries / Q000033:anatomy & histology / Q000473:pathology; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D040081:Protein Array Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013314:Stress, Mechanical; D014664:Vasodilation
D042501:Angiogenic Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger