Extracellular matrix-mediated remodeling and mechanotransduction in large vessels during development and disease

Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence

“…12,[31][32][33] In contrast, the normal vascular media ECM represents a specialized structure, with circumferential layers involving elastin/ fibrillin/fibulins/microfibril glycoprotein-associated matrices (termed elastic lamellae) as well as intermixed and discontinuous basement membrane components (including collagen type IV, laminins, perlecan, nidogens, FN) along with interstitial collagens. 12,[31][32][33][34][35][36] This specialized medial ECM normally suppresses vascular smooth muscle cell (VSMC) activation and promotes VSMC differentiated functions. 8,12,33,37 In addition, these medial ECM matrices are also highly cross-linked by LOX (lysyl oxidase) isoforms and transglutaminases to provide mechanical stability to the highly stressed vascular wall.…”

“…An important general question concerns the nature of ECM remodeling events within vessel walls that occurs following vascular injury responses arising from different disease states (Figure 1). Vascular ECM remodeling events result from (1) leakage and deposition of plasma ECM components into the vessel wall 62,72,81 ; (2) ECM degradation of basement membranes, elastic lamellae or interstitial collagen matrices by proteinases such as MMPs and elastases 58,82–85 ; (3) synthesis and deposition of injury-induced ECM components including cellular FNs, osteopontin, tenascin C, and proteoglycans 8,34,47,49,65 ; and (4) exposure of matricryptic integrin-binding sites and release of matricryptins. 52,53,56 These matricryptic sites include an abundance of RGD sites from unfolded collagens, 51 FNs including plasma FN 86,87 and an alternatively spliced FN isoform (EDA; also EDGIHEL site), 26,88,89 osteopontin (also SVVYGLR and ELVTDFPTDLPAT sites) 90–93 and tenascin C (also AEIGDIEL) 94 allowing for cell injury responses mediated by αv integrins like αvβ3, αvβ1, 95 and αvβ5 (which bind RGD sites), and α5β1 (which binds the RGD site within FN), as well as α9β1 and α4β1 (which bind the matricryptic peptide sequences in parentheses from cellular FN, osteopontin, or tenascin C).…”

“…8,12,33,37 In addition, these medial ECM matrices are also highly cross-linked by LOX (lysyl oxidase) isoforms and transglutaminases to provide mechanical stability to the highly stressed vascular wall. 8,12,[33][34][35] The signaling events controlling the differentiation-promoting influence of this specialized ECM (and possibly its ECMassociated growth factors) are not well understood. The VSMC receptors involved in maintaining the VSMC differentiated state include integrin and nonintegrin ECM receptors, which may include a combination of the elastin receptor complex, 38 as well as integrins with affinity for components of the fibrillin/fibulin-rich matrix, basement membrane proteins, and interstitial collagen components.…”

Mechanistic insight into lysyl oxidase in vascular remodeling and angiogenesis

“…Extracellular matrix (ECM) is critical for structural support to the blood vessels. 2 A properly structured ECM is indispensable for maintenance of the mechanical integrity of the vessels. There is also evidence supporting that increased degradation of elastin, one of the most important ECM components in the aorta, leads to a loss of structural integrity and vessel wall dilation.…”

An In Vivo Model to Study Cell Migration in XYZ-T Dimension Followed by Whole-Mount Re-evaluation

“…A cell seldom migrates alone and interacts often in a leaderfollower pattern with a high dependency on and competition with other cells [1]. Also cells do not migrate in an empty space, and the extracellular environment produced by the cell of interest itself and/or other cells contributes to migration as well [2,3]. It is therefore important to find assays that serve the research question.…”