Basement Membrane Remodelling Controls Endothelial Function in IPAH.

Basement Membrane Remodelling Controls Endothelial Function in IPAH. Am J Respir Cell Mol Biol. 2020 Mar 11;: Authors: Jandl K, Marsh LM, Hoffmann J, Mutgan AC, Baum O, Bloch W, Thekkekara-Puthenparampil H, Kolb D, Sinn K, Klepetko W, Heinemann A, Olschewski A, Olschewski H, Kwapiszewska G Abstract The extracellular matrix (ECM) increasingly emerges as an active driver in several diseases, including idiopathic pulmonary arterial hypertension (IPAH). The basement membrane (BM) is a specialized class of ECM proteins. In pulmonary arteries, the BM is in close contact and direct proximity to vascular cells including endothelial cells. So far, the role of the BM has remained under-investigated in IPAH. Here, we aimed to shed light on the involvement of the BM in IPAH, by addressing its structure, composition and function. On an ultrastructural level, we observed a marked increase in BM thickness in IPAH pulmonary vessels. BM composition was distinct in small and large vessels and altered in IPAH. Proteoglycans were mostly responsible for distinction between smaller and larger vessels, while BM collagens and laminins were more abundantly expressed in IPAH. Type IV collagen and laminin both strengthened endothelial barrier integrity. However, only type IV collagen concentration dependently increased cell adhesion of both donor and IPAH-derived pulmonary arterial endothelial cells (PAEC), and induced nuclear translocation of mechanosensitive...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research