Basement Membrane Remodeling Controls Endothelial Function in Idiopathic Pulmonary Arterial Hypertension.

摘要: The extracellular matrix (ECM) increasingly emerges as an active driver in several diseases, including idiopathic pulmonary arterial hypertension (IPAH). basement membrane (BM) is a specialized class of ECM proteins. In arteries, the BM close contact and direct proximity to vascular cells, endothelial cells. So far, role has remained underinvestigated IPAH. Here, we aimed shed light on involvement IPAH, by addressing its structure, composition, function. On ultrastructural level, observed marked increase thickness IPAH vessels. composition was distinct small large vessels altered Proteoglycans were mostly responsible for distinction between smaller larger vessels, whereas collagens laminins more abundantly expressed Type IV collagen laminin both strengthened barrier integrity. However, only type concentration dependently increased cell adhesion donor IPAH-derived cells (PAECs) induced nuclear translocation mechanosensitive transcriptional coactivator hippo pathway YAP (Yes-activated protein). other hand, caused cytoplasmic retention PAECs. Accordingly, silencing COL4A5 LAMC1, respectively, differentially affected tight junction formation integrity Collectively, our results highlight importance well-maintained homeostasis. By linking changes structure function, here suggest pathogenesis.