PDGF-BB and TGF-{beta}1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress.
Shear stress, especially low shear stress (LowSS), plays an important role in vascular remodeling during atherosclerosis. Endothelial cells (ECs), which are directly exposed to shear stress, convert mechanical stimuli into intracellular signals and interact with the underlying vascular smooth muscle cells (VSMCs). The interactions between ECs and VSMCs modulate the LowSS-induced vascular remodeling. With the use of proteomic analysis, the protein profiles of rat aorta cultured under LowSS (5 dyn/cm(2)) and normal shear stress (15 dyn/cm(2)) were compared. By using Ingenuity Pathway Analysis to identify protein-protein association, a network was disclosed that involves two secretary molecules, PDGF-BB and TGF-β1, and three other linked proteins, lamin A, lysyl oxidase, and ERK 1/2. The roles of this network in cellular communication, migration, and proliferation were further studied in vitro by a cocultured parallel-plate flow chamber system. LowSS up-regulated migration and proliferation of ECs and VSMCs, increased productions of PDGF-BB and TGF-β1, enhanced expressions of lysyl oxidase and phospho-ERK1/2, and decreased Lamin A in ECs and VSMCs. These changes induced by LowSS were confirmed by using PDGF-BB recombinant protein, siRNA, and neutralizing antibody. TGF-β1 had similar influences on ECs as PDGF-BB, but not on VSMCs. Our results suggest that ECs convert the LowSS stimuli into up-regulations of PDGF-BB and TGF-β1, but these two factors play different roles in LowSS-induced vascular remodeling. PDGF-BB is involved in the paracrine control of VSMCs by ECs, whereas TGF-β1 participates in the feedback control from VSMCs to ECs.
Institute of Mechanobiology and Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Ying-Xin
YX
Qi
Jun
J
Jiang
Xiao-Hua
XH
Jiang
Xiao-Dong
XD
Wang
Su-Ying
SY
Ji
Yue
Y
Han
Ding-Kun
DK
Long
Bao-Rong
BR
Shen
Zhi-Qiang
ZQ
Yan
Shu
S
Chien
Zong-Lai
ZL
Jiang
D000818:Animals; D000077214:Becaplermin; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D034904:Lamin Type A / Q000502:physiology; D008084:Lipoxygenase / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D040901:Proteomics; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013314:Stress, Mechanical; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D034904:Lamin Type A; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D008084:Lipoxygenase; D048049:Extracellular Signal-Regulated MAP Kinases
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