Heparin stimulates the proliferation of bovine aortic endothelial cells probably through activation of endogenous basic fibroblast growth factor

Tazawa, Shigeki; Hayakawa, Yumiko; Ishikawa, T.; Niiya, Kenji; Sakuragawa, Nobuo

doi:10.1016/0049-3848(93)90243-h

Cited by 7 publications

(1 citation statement)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Co-culture of VICs with vascular endothelial cells (VECs) isolated from the aorta, or addition of synthetically generated NO, also decrease activation of VICs cultured in osteogenic media (supplemented with dexamethasone) [24]. However, endothelial cells likely secrete multiple beneficial signaling factors (e.g., fibroblast growth factor (FGF) [27] and prostaglandins [28]), which might also suppress VIC activation.…”

Section: Introductionmentioning

confidence: 99%

The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation

Gould¹,

Matherly²,

Smith³

et al. 2014

Biomaterials

View full text Add to dashboard Cite

The effects of valvular endothelial cell (VlvEC) paracrine signaling on VIC phenotype and nodule formation were tested using a co-culture platform with physiologically relevant matrix elasticities and diffusion distance. 100μm thin poly(ethylene glycol) (PEG) hydrogels of 3 to 27 kPa Young’s moduli were fabricated in transwell inserts. VICs were cultured on the gels, as VIC phenotype is known to change significantly within this range, while VlvECs lined the underside of the membrane. Co-culture with VlvECs significantly reduced VIC activation to the myofibroblast phenotype on all gels with the largest percent decrease on the 3 kPa gels (~70%), while stiffer gels resulted in approximately 20–30% decrease. Additionally, VlvECs significantly reduced αSMA protein expression (~2 fold lower) on both 3 and 27 kPa gels, as well as the number (~2 fold lower) of nodules formed on the 27kPa gels. Effects of VlvECs were prevented when nitric oxide (NO) release was inhibited with L-NAME, suggesting that VlvEC produced NO inhibits VIC activation. Withdrawal of L-NAME after 3, 5, and 7 days with restoration of VlvEC NO production for 2 additional days led to a partial reversal of VIC activation (~25% decrease). A potential mechanism by which VlvEC produced NO reduced VIC activation was studied by inhibiting initial and mid-stage cGMP pathway molecules. Inhibition of soluble guanylyl cyclase (sGC) with ODQ or protein kinase G (PKG) with RBrcGMP or stimulation of Rho kinase (ROCK) with LPA, abolished VlvEC effects on VIC activation. This work contributes substantially to the understanding of the valve endothelium’s role in preventing VIC functions associated with aortic valve stenosis initiation and progression.

show abstract

Section: Introductionmentioning

confidence: 99%