Oral Resolvin D1 attenuates early inflammation but not intimal hyperplasia in a rat carotid angioplasty model

Research output: Contribution to journalArticle

Authors

  • Giorgio Mottola
  • Evan C. Werlin
  • Bian Wu
  • Mian Chen
  • Anuran Chatterjee
  • Melinda S. Schaller
  • Michael S. Conte

External Institution(s)

  • University of California at San Francisco

Details

Original languageEnglish (US)
Article number106401
JournalProstaglandins and Other Lipid Mediators
Volume146
StatusPublished - Feb 2020
Peer-reviewedYes

Abstract

Inflammation ensuing from vascular injury promotes intimal hyperplasia (IH) and restenosis. Resolvin D1 (RvD1) is a lipid mediator that attenuates IH in vivo when delivered locally to the vessel wall in animal models. We tested the hypothesis that peri-procedural oral administration of RvD1 could blunt the local inflammatory response to angioplasty, and attenuate downstream IH. Carotid angioplasty was performed on rats fed with either RvD1 or vehicle through oral gavage, starting one day prior to injury until post-operative day (POD) 3 or 14 when arteries were harvested. To study pharmacokinetics and bioactivity of oral RvD1, we measured plasma RvD1 by ELISA, whole blood phagocytosis activity using flow cytometry, and cAMP levels in the thoracic aorta by ELISA. Carotid arteries were harvested on POD3 for staining (anti-CD45, anti-Myeloperoxidase (MPO), anti-Ki67 or dihydroethidium (DHE) for reactive oxygen species), mRNA expression of target genes (quantitative RT-PCR), or on POD14 for morphometry (elastin stain). RvD1 plasma concentration peaked 3 h after gavage in rats, at which point we concurrently observed an increase in circulating monocyte phagocytosis activity and aortic cAMP levels in RvD1-treated rats vs. vehicle. Oral RvD1 attenuated local arterial inflammation after angioplasty by reducing CD45+, MPO+, Ki67+ cells, and DHE staining intensity. Oral RvD1 also reduced the expression of several pro-inflammatory genes within the injured vessels. However, oral RvD1 did not significantly reduce IH. Oral RvD1 attenuated acute inflammation within the arterial wall after angioplasty in rats, but did not significantly affect IH.

    Research areas

  • Angioplasty, Inflammation, Intimal hyperplasia, Resolvin D1, Restenosis

Citation formats

APA

Mottola, G., Werlin, E. C., Wu, B., Chen, M., Chatterjee, A., Schaller, M. S., & Conte, M. S. (2020). Oral Resolvin D1 attenuates early inflammation but not intimal hyperplasia in a rat carotid angioplasty model. Prostaglandins and Other Lipid Mediators, 146, [106401]. https://doi.org/10.1016/j.prostaglandins.2019.106401

Harvard

Mottola, G, Werlin, EC, Wu, B, Chen, M, Chatterjee, A, Schaller, MS & Conte, MS 2020, 'Oral Resolvin D1 attenuates early inflammation but not intimal hyperplasia in a rat carotid angioplasty model', Prostaglandins and Other Lipid Mediators, vol. 146, 106401. https://doi.org/10.1016/j.prostaglandins.2019.106401