AIMS: To investigate apelin-APJ (angiotensin receptor-like 1) signalling in vascular remodelling, we have examined the pathophysiological response to carotid ligation in apelin knockout mice. METHODS AND RESULTS: Apelin null animals compared with wild-type mice had significantly decreased neointimal lesion area (1.17 +/- 0.17 vs. 3.33 +/- 1.04 x 10(4) microm(2), P < 0.05) and intima/media ratio (0.81 +/- 0.23 vs. 1.49 +/- 0.44, P < 0.05), averaged over four sites 0.5-2 mm from the ligation. Exogenous apelin infusion rescued the apelin-KO phenotype, promoting neointima formation in the null animals. Apelin null animals showed decreased smooth muscle positive area in the neointima (82.3 +/- 2.4 vs. 63.9 +/- 8.4, P < 0.05), and a smaller percentage BrdU positive cells in the neointima and media (11.06 +/- 1.00 vs. 6.53 +/- 0.86, P < 0.05). Apelin mRNA expression increased initially (5.2-fold, P < 0.01) followed by increased apelin receptor expression (10.1-fold, P < 0.05) in the ligated artery. Cytochemistry studies localized apelin expression to luminal endothelial cells and apelin receptor upregulation to smooth muscle cells (SMC) in the media and neointima. In vitro experiments with cultured rat aortic SMC revealed that apelin stimulation increased migration. In contrast to the increased expression of apelin and apelin receptor in carotid remodelling, expression was not upregulated in the apoE high fat model, and correlated with the known disease-inhibitory effect in this model. CONCLUSION: These data suggest that increased apelin receptor expression by SMC provides a paracrine pathway in injured vessels that allows endothelial-derived apelin to stimulate their division and migration into the neointima.
AIMS: To investigate apelin-APJ (angiotensin receptor-like 1) signalling in vascular remodelling, we have examined the pathophysiological response to carotid ligation in apelin knockout mice. METHODS AND RESULTS:Apelin null animals compared with wild-type mice had significantly decreased neointimal lesion area (1.17 +/- 0.17 vs. 3.33 +/- 1.04 x 10(4) microm(2), P < 0.05) and intima/media ratio (0.81 +/- 0.23 vs. 1.49 +/- 0.44, P < 0.05), averaged over four sites 0.5-2 mm from the ligation. Exogenous apelin infusion rescued the apelin-KO phenotype, promoting neointima formation in the null animals. Apelin null animals showed decreased smooth muscle positive area in the neointima (82.3 +/- 2.4 vs. 63.9 +/- 8.4, P < 0.05), and a smaller percentage BrdU positive cells in the neointima and media (11.06 +/- 1.00 vs. 6.53 +/- 0.86, P < 0.05). Apelin mRNA expression increased initially (5.2-fold, P < 0.01) followed by increased apelin receptor expression (10.1-fold, P < 0.05) in the ligated artery. Cytochemistry studies localized apelin expression to luminal endothelial cells and apelin receptor upregulation to smooth muscle cells (SMC) in the media and neointima. In vitro experiments with cultured rat aortic SMC revealed that apelin stimulation increased migration. In contrast to the increased expression of apelin and apelin receptor in carotid remodelling, expression was not upregulated in the apoE high fat model, and correlated with the known disease-inhibitory effect in this model. CONCLUSION: These data suggest that increased apelin receptor expression by SMC provides a paracrine pathway in injured vessels that allows endothelial-derived apelin to stimulate their division and migration into the neointima.
Authors: D K Lee; R Cheng; T Nguyen; T Fan; A P Kariyawasam; Y Liu; D H Osmond; S R George; B F O'Dowd Journal: J Neurochem Date: 2000-01 Impact factor: 5.372
Authors: Mary M Chen; Euan A Ashley; David X F Deng; Anya Tsalenko; Alicia Deng; Raymond Tabibiazar; Amir Ben-Dor; Brett Fenster; Eugene Yang; Jennifer Y King; Michael Fowler; Robert Robbins; Frances L Johnson; Laurakay Bruhn; Theresa McDonagh; Henry Dargie; Zohar Yakhini; Philip S Tsao; Thomas Quertermous Journal: Circulation Date: 2003-09-08 Impact factor: 29.690
Authors: Yvonne P de Visser; Frans J Walther; El Houari Laghmani; Arnoud van der Laarse; Gerry T M Wagenaar Journal: Am J Respir Crit Care Med Date: 2010-07-09 Impact factor: 21.405
Authors: Andrew G Masoud; Jiaxin Lin; Abul K Azad; Maikel A Farhan; Conrad Fischer; Lin F Zhu; Hao Zhang; Banu Sis; Zamaneh Kassiri; Ronald B Moore; Daniel Kim; Colin C Anderson; John C Vederas; Benjamin A Adam; Gavin Y Oudit; Allan G Murray Journal: J Clin Invest Date: 2020-01-02 Impact factor: 14.808
Authors: Jochen Dutzmann; Lena Marie Bode; Katrin Kalies; Laura Korte; Kai Knöpp; Frederik Julius Kloss; Mirja Sirisko; Claudia Pilowski; Susanne Koch; Heiko Schenk; Jan-Marcus Daniel; Johann Bauersachs; Daniel G Sedding Journal: Front Cardiovasc Med Date: 2022-08-09