Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21cip1 in vascular remodelling during vein arterialization in the rat

Thaiz Ferraz Borin, Ayumi Aurea Miyakawa, Leandro Cardoso, Luciano De Figueiredo Borges, Giovana Aparecida Gonçalves, Jose Eduardo Krieger

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Neo-intima development and atherosclerosis limit long-term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, and key molecular events during vein arterialization resemble the human vein graft adaptation. Right jugular vein was surgically connected to carotid artery and observed up to 90 days. Morphometry demonstrated gradual thickening of the medial layer and important formation of neo-intima with deposition of smooth muscle cells (SMC) in the subendothelial layer from day 7 onwards. Transmission electron microscopy showed that SMCs switch from the contractile to synthetic phenotype on day 3 and new elastic lamellae formation occurs from day 7 onwards. Apoptosis markedly increased on day 1, while α-actin immunostaining for SMC almost disappeared by day 3. On day 7, cell proliferation reached the highest level and cellular density gradually increased until day 90. The relative magnitude of cellular changes was higher in the intima vs. the media layer (100 vs. 2 times respectively). Cyclin-dependent kinase inhibitors (CDKIs) p27Kip1 and p16 INKA remained unchanged, whereas p21Cip1 was gradually downregulated, reaching the lowest levels by day 7 until day 90. Taken together, these data indicate for the first time that p21Cip1 is the main CDKI protein modulated during the arterialization process the rat model of vein arterialization that may be useful to identify and validate new targets and interventions to improve the long-term patency of vein grafts.

Original languageEnglish (US)
Pages (from-to)328-337
Number of pages10
JournalInternational Journal of Experimental Pathology
Volume90
Issue number3
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

Keywords

  • Animal model
  • Vein graft
  • Venous arterialization

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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