A heparin-rosuvastatin-loaded P(LLA-CL) nanofiber-covered stent inhibits inflammatory smooth-muscle cell viability to reduce in-stent stenosis and thrombosis.

Abstract

BACKGROUND:

An endovascular covered-stent has unique advantages in treating complex intracranial aneurysms; however, in-stent stenosis and late thrombosis have become the main factors affecting the efficacy of covered-stent treatment. Smooth-muscle-cell phenotypic modulation plays an important role in late in-stent stenosis and thrombosis. Here, we determined the efficacy of using covered stents loaded with drugs to inhibit smooth-muscle-cell phenotypic modulation and potentially lower the incidence of long-term complications.

METHODS:

Nanofiber-covered stents were prepared using coaxial electrospinning, with the core solution prepared with 15% heparin and 20 µM rosuvastatin solution (400: 100 µL), and the shell solution prepared with 120 mg/mL hexafluoroisopropanol. We established a rabbit carotid-artery aneurysm model, which was treated with covered stents. Angiography and histology were performed to evaluate the therapeutic efficacy and incidence rate of in-stent stenosis and thrombosis. Phenotype, function, and inflammatory factors of smooth-muscle cells were studied to explore the mechanism of rosuvastatin action in smooth-muscle cells.

RESULT:

Heparin-rosuvastatin-loaded nanofiber scaffold mats inhibited the proliferation of synthetic smooth-muscle cells, and the nanofiber-covered stent effectively treated aneurysms in the absence of notable in-stent stenosis. Additionally, in vitro experiments showed that rosuvastatin inhibited the smooth-muscle-cell phenotypic modulation of platelet-derived growth factor-BB induction and decreased synthetic smooth-muscle-cell viability, as well as secretion of inflammatory cytokines.

CONCLUSION:

Rosuvastatin inhibited the abnormal proliferation of synthetic smooth-muscle cells, and heparin-rosuvastatin-loaded covered stents reduced the incidence of stenosis and late thrombosis, thereby improving the healing rates of stents used for aneurysm treatment.

• Authors: Yingjun Liu, Peixi Liu, Yaying Song, Sichen Li, Yuan Shi, Kai Quan, Guo Yu, Peiliang Li, Qingzhu An, Wei Zhu
• Journal: Journal of nanobiotechnology (J Nanobiotechnology) Vol. 19 Issue 1 Pg. 123 (Apr 29 2021) ISSN: 1477-3155 [Electronic] England
• PMID: 33926468 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Polyesters
• poly(lactic acid-co-epsilon-caprolactone)
• Rosuvastatin Calcium
• Heparin

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Constriction, Pathologic (drug therapy)
• Cytokines (metabolism)
• Heparin (pharmacology)
• Intracranial Aneurysm (therapy)
• Male
• Mice
• Muscles (drug effects)
• Nanofibers (chemistry)
• Polyesters (chemistry, pharmacology)
• Rabbits
• Rosuvastatin Calcium (pharmacology)
• Stents
• Thrombosis (drug therapy, pathology)