Laminin isoforms in endothelial and perivascular basement membranes

Abstract

Laminins, one of the major functional components of basement membranes, are found underlying endothelium, and encasing pericytes and smooth muscle cells in the vessel wall. Depending on the type of blood vessel (capillary, venule, postcapillary venule, vein or artery) and their maturation state, both the endothelial and mural cell phenotype vary, with associated changes in laminin isoform expression. Laminins containing the α4 and α5 chains are the major isoforms found in the vessel wall, with the added contribution of laminin α2 in larger vessels. We here summarize current data on the precise localization of these laminin isoforms and their receptors in the different layers of the vessel wall, and their potential contribution to vascular homeostasis.

Figure 1. Schematic representation of the cellular and extracellular matrix layers that constitute the vessel wall of arterioles, capillaries, postcapillary venules and venules. Basement membranes underlie the endothelial cell monolayer and ensheath pericytes and smooth muscle cells, and vary in their laminin α chain expression and localization (summarized in the top panel). In arterioles and venules the interstitial matrix interconnects the different cellular and BM layers. *Laminin α2 has not been systematically studied in vascular smooth muscle BMs, but has been reported to occur in smooth muscle of the aorta and carotid arteries.

Figure 2. Model of laminin isoforms found in vascular BMs. Potential integrin and non-integrin receptors for each laminin isoform and their approximate interaction sites on the laminin α chains are shown.

Figure 3. Immunofluorescence staining for laminin α5, as a BM marker, in capillaries and arterioles. Staining for laminin α5 together with (A) desmin, to mark pericytes, or (B) PECAM-1, to mark the endothelium, reveals pericyte cell bodies (arrows) and their extensive processes embedded in the endothelial cell BM. Double staining for laminin α5 and α-smooth muscle actin (α-SMA) (C) reveals the BM of the individual smooth muscle cells (arrowhead) enwrapping arterioles. Scale bars are 20 μm and 5 μm in the insets.

Figure 4 (See opposite page). Schematic representation of laminin functions in the endothelial and smooth muscle layers of the vessel wall. (A) In postcapillary venules, the absence of laminin α5 in the endothelial BM defines sites of leukocyte extravasation. Small (resistance) arterioles (B and C) are responsible for controlling vessel diameter in response to hemodynamics, where integrin-mediated anchorage to laminins in the endothelial BM via focal adhesions are implicated in shear sensing and transduction of signals to the underlying smooth muscle cells (B). (C) Vascular smooth muscle responds to shear and intraluminal pressure changes by contraction or relaxation, which requires firm anchorage between the individual vSMC and their BM. Vessel injury can induce changes in vSMC phenotype from a contractile to a dedifferentiated non-contractile phenotype, which is associated with changes in the surrounding BM and interstitial matrix.