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

Autor(es)

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

Afiliação do(s) autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Experimental Pathology; v. 90, n. 3, p. 328-337, June 2009.
• Área do conhecimento: Ciências Biológicas - Fisiologia
• Notas: O artigo consta como produto de três processos: 00/09485-7 em nome de Ayumi Aurea Miyakawa; 01/00009-0 em nome de Eduardo Moacyr Krieger; e 03/01828-0 em nome de Thaiz Ferraz Borin
• Citações Web of Science: 16
• Assunto(s): Sistema cardiovascular Coração Veias Artérias Transplantes

Resumo

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)

• Processo FAPESP: 03/01828-0 - Genes diferentemente expressos em modelo de arterialização de enxerto venoso no rato: identificação e caracterização de novos alvos terapêuticos
• Beneficiário: Thaiz Ferraz Borin
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 01/00009-0 - Estudo integrado da hipertensão arterial: caracterização molecular e funcional do sistema cardiovascular
• Beneficiário: Eduardo Moacyr Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 00/09485-7 - Identificacao de genes com expressao diferenciada em veia safena submetida ao regime arterial.
• Beneficiário: Ayumi Aurea Miyakawa Yamaguchi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado