Ang II–stimulated migration of vascular smooth muscle cells is dependent on LR11 in mice

Abstract

Medial-to-intimal migration of

The Soluble Form of LR11 Protein Is a Regulator of Hypoxia-induced, Urokinase-type Plasminogen Activator Receptor (uPAR)-mediated Adhesion of Immature Hematological Cells

“…1). Together with the previous observations that sLR11 is produced only by immature SMCs and not in mature SMCs in atherosclerotic arteries (21) and that high levels of LR11 mRNA are expressed in human CD34 ϩ CD38 Ϫ immature hematopoietic progenitors (26), sLR11 released from immature cells may strengthen cell attachment to other stromal cells or extracellular matrices. In this context, preliminary results suggest that sLR11 is a potent enhancer of TNF-␣-induced attachment of hematological cells to stromal cells in response to G-CSF treatment.…”

“…In this context, we showed previously that sLR11 derived from the cell surface enhances cell adhesion through the activation of uPAR and integrin-mediated signals (21,41,42). On the other hand, LR11 in intracellular vesicles (SorLA) is important for the intracellular traffic of amyloid␤ protein in neurons (43), and single nucleotide polymorphisms in the LR11/SORL1 gene and/or sLR11 levels in the cerebrospinal fluid have been reported to be a prospective marker of Alzheimer disease (44,45).…”

“…Complex-sLR11 enhances adhesion of SMCs through signaling via uPAR and integrins (21), and hypoxia leads to increased expression of uPAR in cultured hematological and other cells (19,36,37). Therefore, we examined whether uPAR also is a player in the sLR11-mediated adhesion of hematological cells.…”

“…We have identified and characterized a regulator of uPAR function, LR11 (also called SorLA or SORL1), in vascular smooth muscle cells (SMCs) (20,21). LR11 is a type I membrane protein, from which a large soluble extracellular part, sLR11, is released by proteolytic shedding (20,(22)(23)(24).…”

Protein sorting gone wrong – VPS10P domain receptors in cardiovascular and metabolic diseases

“…The encoding gene had been mapped as a pro-atherogenic locus in inbred strains of mice 16 . The relevance of SORLA for atherosclerotic processes was further substantiated by correlating circulating levels of the shedded ectodomain (considered as a diagnostic marker of receptor levels in tissues) with intima-media thickness in dyslipidemic subjects 17 , with coronary artery disease 18 , and with acute coronary syndrome 19 . Genetic An alternative model suggests a more direct role for SORLA in atherosclerotic processes in the vessel wall.…”