Mechanobiological Mechanism Of Crosstalk Between Vascular Smooth Muscle Cells And Endothelium Cells

Vascular remodeing is the fundamental pathological mechanism andprocess of cardiovascular diseases. Mechanical factor is an importantregulator in this process. Endothelial cells (ECs) have close relationshipwith vascular smooth muscle cells (VSMCs) and their cross-talk plays avital role in vascular remodeling. However, the mechanobiologicalmechanism of crosstalk between the ECs and the VSMCs undermechanical force stimulus has not yet been established.In our previous vascular proteomics study, the protein expressionprofiles of rat aortas cultured under normal shear stress (NSS,15dyn/cm2)and low shear stress (LowSS,5dyn/cm2) were compared. By usingIngenuity Pathway Analysis to identify protein–protein association, thenetwork that centred on PDGF-BB and TGF-β1had been predicted. AnECs and VSMCs co-culture system was established, and LowSS wasapplyed on ECs by a parallel plate flow-chamber. The expression ofPDGF-BB and TGF-β1increased, the expression of LaminA decreasedand the expressions of LOX and phosphor-ERK1/2were attenuated in ECs and VSMCs. Recombinate proteins of PDGF-BB and TGF-β1showed the similar effects. RNA interference target to PDGF-BB orneutralization antibody blocking in ECs caused the changes in VSMCssubjected to LowSS attenuated; RNA interference target to TGF-β1orneutralization antibody blocking in ECs showed no effects on VSMCssubjected to LowSS; RNA interference target to PDGF-BB orneutralization antibody blocking in VSMCs showed no effects on ECssubjected to LowSS; RNA interference target to TGF-β1or neutralizationantibody blocking in VSMCs discharged the changes in ECs subjected toLowSS. The data demonstrate that PDGF-BB and TGF-β1play thedifferent roles in LowSS induced the cross-talk between ECs and VSMCs.ECs regulate function of VSMC by secreting PDGF-BB and VSMCsfeedck control ECs by secreting TGF-β1.The function of Rab28was also investigated in the cross-talk ofvascular cells on basis of our previous vascular proteomics study. Wefound Rab28expression elevated in the carotid arteries of hypertensiverat. High cyclic strain increased Rab28expression in VSMCs. Mediaconditioned by VSMCs were transferred to cultivate ECs. Expression ofRab28in ECs also increased. It was identified angiotensin II (Ang II)concentration in the conditioned media from VSMCs undergone highcyclic strain was higher than in which under normal cyclic strain. In staticECs, NF-кB and Rab28were all in the cytoplasm and co-localized; in thecell stimulated with Ang II, NF-кB and Rab28were largely in the nucleus.These data demonstrated Rab28may regulate NF-кB nuclear transport. Down-regulation of Rab28expression by RNA interference attenuatedNF-κB Phosphorylation. Then, inhibition of NF-κB activation resulted indecline Rab28production. The results demonstrated Rab28influencesNF-κB activation and NF-κB feed-back regulates Rab28expression.In the present study, the roles of PDGF-BB and TGF-β1in thecross-talk of ECs and VSMCs subjected to LowSS and the function ofRab28in the interaction of ECs and VSMCs subjected to high cyclicstrain were investigated. The data provided some novel knowledge formechanobiological mechanism of vascular remodeling induced bymechanical forces and potential orientation of relevant diseasesinvestigation.