Journal article

Publication year: 2011

Pages: 276-286

Journal: Cardiovascular Research

Volume number: 92

Issue number: 2

ISSN: 0008-6363

Open access status: Bronze

DOI Link: https://doi.org/10.1093/cvr/cvr213

Publisher: Oxford University Press

Abstract: 

Aims Intermedin (IMD) is a novel member of the calcitonin gene-related peptide family, which acts via calcitonin receptor-like receptors (CLRs), mediating activation of cAMP signalling. The main objective of the present study was to analyse the molecular mechanisms of the differential effects of IMD on the macromolecule permeability of endothelial cells of different vascular beds.

Methods and results Here we demonstrate that IMD increases permeability of rat coronary microvascular endothelial cells (RCECs) and reduces permeability of human umbilical vein endothelial cells (HUVECs) and rat aortic endothelial cells via CLRs and cAMP. Intermedin causes a derangement of the actin cytoskeleton accompanied by loss of vascular endothelial cadherin (VE-cadherin) in RCECs, while it causes a rearrangement of the actin cytoskeleton and VE-cadherin at cell-cell junctions in HUVECs. Intermedin inactivates the RhoA/Rho-kinase (Rock) pathway in both cell types; however, it inactivates Rac1 in RCECs but not in HUVECs. Inhibition and rescue experiments demonstrate that both RhoA and Rac1 are required for the RCEC barrier stability, while in HUVECs the inhibition of RhoA/Rock signalling does not interfere with basal permeability.

Conclusion The opposite effects of IMD on permeability of RCECs and HUVECs are due to differential regulation of actin cytoskeleton dynamics via RhoA and Rac1. Moreover, Rac1 activity is regulated by the RhoA/Rock pathway in RCECs but not in HUVECs.

Harvard Citation style: Aslam, M., Guenduez, D., Schuler, D., Li, L., Sharifpanah, F., Sedding, D., et al. (2011) Intermedin induces loss of coronary microvascular endothelial barrier via derangement of actin cytoskeleton: role of RhoA and Rac1, Cardiovascular Research, 92(2), pp. 276-286. https://doi.org/10.1093/cvr/cvr213

APA Citation style: Aslam, M., Guenduez, D., Schuler, D., Li, L., Sharifpanah, F., Sedding, D., Piper, H., & Noll, T. (2011). Intermedin induces loss of coronary microvascular endothelial barrier via derangement of actin cytoskeleton: role of RhoA and Rac1. Cardiovascular Research. 92(2), 276-286. https://doi.org/10.1093/cvr/cvr213