Intermittent hypoxia changes the interaction of the kinin-VEGF system and impairs myocardial angiogenesis in the hypertrophic heart

Autor(es)

Visniauskas, Bruna ^[1] ; Perry, Juliana C. ^[1] ; Gomes, Guiomar N. ^[2] ; Nogueira-Pedro, Amanda ^[3] ; Paredes-Gamero, Edgar J. ^[3] ; Tufik, Sergio ^[1] ; Chagas, Jair R. ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Psicobiol, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Fisiol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biofis, Rua Pedro de Toledo 669, 7andar, BR-04044020 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHYSIOLOGICAL REPORTS; v. 9, n. 9 MAY 2021.
• Citações Web of Science: 0

Resumo

Intermittent hypoxia (IH) is a feature of obstructive sleep apnea (OSA), a condition highly associated with hypertension-related cardiovascular diseases. Repeated episodes of IH contribute to imbalance of angiogenic growth factors in the hypertrophic heart, which is key in the progression of cardiovascular complications. In particular, the interaction between vascular endothelial growth factor (VEGF) and the kallikrein-kinin system (KKS) is essential for promoting angiogenesis. However, researchers have yet to investigate experimental models of IH that reproduce OSA, myocardial angiogenesis, and expression of KKS components. We examined temporal changes in cardiac angiogenesis in a mouse IH model. Adult male C57BI/6 J mice were implanted with Matrigel plugs and subjected to IH for 1-5 weeks with subsequent weekly histological evaluation of vascularization. Expression of VEGF and KKS components was also evaluated. After 3 weeks, in vivo myocardial angiogenesis and capillary density were decreased, accompanied by a late increase of VEGF and its type 2 receptor. Furthermore, IH increased left ventricular myocardium expression of the B2 bradykinin receptor, while reducing mRNA levels of B1 receptor. These results suggest that in IH, an unexpected response of the VEGF and KKS systems could explain the reduced capillary density and impaired angiogenesis in the hypoxic heart, with potential implications in hypertrophic heart malfunction. (AU)

• Processo FAPESP: 12/02123-0 - Interação do sistema calicreínas-cininas e fator de crescimento vascular endotelial (VEGF) em modelos animais de hipóxia intermitente
• Beneficiário: Bruna Visniauskas
• Modalidade de apoio: Bolsas no Brasil - Doutorado