Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat

Author(s)

Borin, Thaiz Ferraz ^[1] ; Miyakawa, Ayumi Aurea ^[1] ; Cardoso, Leandro ^[1] ; Borges, Luciano de Figueiredo ^[1] ; Goncalves, Giovana Aparecida ^[1] ; Krieger, Jose Eduardo ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol, Inst Heart InCor, LIM 13, BR-05403000 Sao Paulo - Brazil

• Document type: Journal article
• Source: International Journal of Experimental Pathology; v. 90, n. 3, p. 328-337, June 2009.
• Field of knowledge: Biological Sciences - Physiology
• Web of Science Citations: 16

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 á-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 p16INKA 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. (AU)

• FAPESP's process: 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system
• Grantee: Eduardo Moacyr Krieger
• Support Opportunities: Research Projects - Thematic Grants