Abstract
Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.
Highlights
Pulmonary arterial hypertension (PAH) is a rare but severe pulmonary vascular disease with poor prognosis and survival
Type IV collagens directly bind to cell surface receptors, such as integrins or discoidin domain receptors, and initiate signaling pathways that are often associated with proliferation, migration, and polarity in order to sustain vascular stability [47,48]
When exposed to LN-421 compared to LN-411, endothelial cells (ECs) show a more activated phenotype, which is recapitulated by increased adhesion, migration, tube formation, and the secretion of thrombospondin-2 and fibroblast growth factor (FGF) [70]
Summary
Pulmonary arterial hypertension (PAH) is a rare but severe pulmonary vascular disease with poor prognosis and survival. The major BM components are laminins, type IV collagens, and BM proteoglycans (BM heparan sulfate proteoglycans and other BM glycoproteins) [15] In addition to their structural function, accumulating evidence indicates that BM proteins actively modulate cellular processes. This is accomplished in multiple ways: First, all major components can directly interact with cells via specific cell surface receptors, thereby influencing the cell shape, cell motility, proliferation, and intracellular signaling programs [16,17]. We will use the vast knowledge of the BM on endothelial function in general, summarize the accumulating evidence of the BM involvement in pulmonary vascular remodeling, and provide an outlook for future investigations in the PH field
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