Inhibition effect of tacrolimus and platelet-derived growth factor-BB on restenosis after vascular intimal injury.

Abstract

Excessive proliferation and migration of vascular smooth muscle cells(VSMCs) and delayed proliferation and migration of endothelial cells(ECs) were the main cause of restenosis after endovascular interventional therapy. Since tacrolimus has proved to be more sensitive to inhibiting VSMCs' proliferation,and platelet-derived growth factor-BB(PDGF-BB) benefitted ECs' and VSMCs' proliferation, this study was aimed to identify combined effect of tacrolimus and PDGF-BB, investigate any mechanisms underneath and demonstrate combined effect of two drugs in vivo. As the results showed we confirmed differential effect of PDGF-BB and tacrolimus on ECs and VSMCs. On the concentration level of 2-5μg/ml tacrolimus plus 10ng/ml PDGF-BB, combination of drugs could effectively promote ECs proliferation and migration, and meanwhile inhibit VSMCs proliferation and migration, and the inhibition of p-mTOR's expression within VSMCs played an important role in this differentiated effect. Raising concentration level of PDGF-BB would weaken inhibitory effect of tacrolimus on both kinds of cell. For injured intima, the mix solution of two drugs could promote intima healing and suppress excessive intimal hyperplasia.

• Authors: Xu Ma, Chunyu Jiang, Yuehua Li, Lishuai Feng, Jingjing Liu, Jianbo Wang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 93 Pg. 180-189 (Sep 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28633129 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Proto-Oncogene Proteins c-sis
• Becaplermin
• TOR Serine-Threonine Kinases
• Tacrolimus

Topics

• Animals
• Becaplermin
• Cell Differentiation (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Graft Occlusion, Vascular (drug therapy, metabolism)
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-sis (pharmacology)
• Rats
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tacrolimus (pharmacology)
• Tunica Intima (drug effects, metabolism)
• Vascular System Injuries (drug therapy, metabolism)