Lysyl oxidase: an oxidative enzyme and effector of cell function

Lucero, Héctor A.; Kagan, Herbert M.

doi:10.1007/s00018-006-6149-9

Cited by 505 publications

(497 citation statements)

References 82 publications

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“…These data indicate that SHR TA VSMCs exhibit a regulation of LOX at gene expression and proteolytic levels. Second, In contrast to previous studies, instead of a single mature‐LOX isoform as observed in most other tissues (Barker, Cox & Erler, 2012; Lopez et al., 2009; Lucero & Kagan, 2006; Payne, Hendrix & Kirschmann, 2007), we detected two forms of mature‐LOX in rat aortic VSMCs. This finding could imply that a unique mechanism may be involved in the proteolytic processing of LOX, by which different sites of pro‐LOX may be targeted and result in two different sizes of mature‐LOX.…”

Section: Discussionmentioning

confidence: 63%

Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

Hays

Zhou

et al. 2018

Aging Cell

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SummaryAortic stiffening is an independent risk factor that underlies cardiovascular morbidity in the elderly. We have previously shown that intrinsic mechanical properties of vascular smooth muscle cells (VSMCs) play a key role in aortic stiffening in both aging and hypertension. Here, we test the hypothesis that VSMCs also contribute to aortic stiffening through their extracellular effects. Aortic stiffening was confirmed in spontaneously hypertensive rats (SHRs) vs. Wistar‐Kyoto (WKY) rats in vivo by echocardiography and ex vivo by isometric force measurements in isolated de‐endothelized aortic vessel segments. Vascular smooth muscle cells were isolated from thoracic aorta and embedded in a collagen I matrix in an in vitro 3D model to form reconstituted vessels. Reconstituted vessel segments made with SHR VSMCs were significantly stiffer than vessels made with WKY VSMCs. SHR VSMCs in the reconstituted vessels exhibited different morphologies and diminished adaptability to stretch compared to WKY VSMCs, implying dual effects on both static and dynamic stiffness. SHR VSMCs increased the synthesis of collagen and induced collagen fibril disorganization in reconstituted vessels. Mechanistically, compared to WKY VSMCs, SHR VSMCs exhibited an increase in the levels of active integrin β1‐ and bone morphogenetic protein 1 (BMP1)‐mediated proteolytic cleavage of lysyl oxidase (LOX). These VSMC‐induced alterations in the SHR were attenuated by an inhibitor of serum response factor (SRF)/myocardin. Therefore, SHR VSMCs exhibit extracellular dysregulation through modulating integrin β1 and BMP1/LOX via SRF/myocardin signaling in aortic stiffening.

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Section: Discussionmentioning

confidence: 63%

Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

Hays

Zhou

et al. 2018

Aging Cell

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“…Numerous other proteins associate with microfibrils or with elastin itself, including the microfibril associated glycoproteins (MAGPs), fibulins and EMILIN-1 (for a complete list see Kielty et al, 2002). Based on ultrastructural studies, microfibrils are thought to provide a scaffold that facilitates elastin molecular alignment and subsequent cross-linking, which is catalyzed by one or more members of the lysyl oxidase (LOX) gene family (Csiszar, 2001;Kagan and Li, 2003;Lucero and Kagan, 2006).…”

Section: Elastic Fiber Componentsmentioning

confidence: 99%

New insights into elastic fiber assembly

Wagenseil

Mecham

2007

Birth Defects Research Pt C

357

354

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Elastic fibers provide recoil to tissues that undergo repeated stretch, such as the large arteries and lung. These large extracellular matrix (ECM) structures contain numerous components, and our understanding of elastic fiber assembly is changing as we learn more about the various molecules associated with the assembly process. The main components of elastic fibers are elastin and microfibrils. Elastin makes up the bulk of the mature fiber and is encoded by a single gene. Microfibrils consist mainly of fibrillin, but also contain or associate with proteins such as microfibril associated glycoproteins (MAGPs), fibulins, and EMILIN-1. Microfibrils were thought to facilitate alignment of elastin monomers prior to cross-linking by lysyl oxidase (LOX). We now know that their role, as well as the overall assembly process, is more complex. Elastic fiber formation involves elaborate spatial and temporal regulation of all of the involved proteins and is difficult to recapitulate in adult tissues. This report summarizes the known interactions between elastin and the microfibrillar proteins and their role in elastic fiber assembly based on in vitro studies and evidence from knockout mice. We also propose a model of elastic fiber assembly based on the current data that incorporates interactions between elastin, LOXs, fibulins and the microfibril, as well as the pivotal role played by cells in structuring the final functional fiber. Birth Defects Research (Part C) 81:229-240,

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“…5 Indeed, recent findings revealed that LOX family proteins markedly influence cell behavior, including chemotactic responses, cell growth and intracellular signaling and transcription. 1,26-29 Recently, Eliades et al reported that LOX inhibition with BAPN reduces downstream signaling of platelet-derived growth factor receptor, including activation of Akt and ERK1/2 pathways, and diminishes the proliferative effect of the platelet-derived growth factor receptor on the megakaryocyte lineage, 30 suggesting that LOX proteins have a functional role in growth factor receptor signaling and cell growth.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 These proteins have a conserved C-terminal region corresponding to the catalytic domain, which includes the lysine tyrosylquinone cofactor, the copper-binding site and the cytokine receptor-like domain. 5 They exhibit different in vivo expression patterns and have different biological roles, including extracellular matrix stabilization, cell proliferation, cell growth and intracellular signal response. 5 In 2006, we reported that LOXL-1 mRNA was upregulated in pressure overloaded hypertrophied hearts induced by abdominal aortic constriction (AAC).…”

Section: Introductionmentioning

confidence: 99%

“…5 They exhibit different in vivo expression patterns and have different biological roles, including extracellular matrix stabilization, cell proliferation, cell growth and intracellular signal response. 5 In 2006, we reported that LOXL-1 mRNA was upregulated in pressure overloaded hypertrophied hearts induced by abdominal aortic constriction (AAC). 6 Since then, similar findings have been reported in animal models of diet-induced fibrotic hearts, cardiac remodeling of diet-induced metabolic syndrome and hypertrophied hearts of spontaneously hypertensive rats, [7][8][9] as well as in patients with dilated cardiomyopathy and heart failure.…”

Section: Introductionmentioning

confidence: 99%

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Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice

et al. 2012

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Lysyl oxidase (LOX) and LOX-like protein-1 (LOXL-1) are extracellular matrix-embedded amine oxidases that have critical roles in the cross-linking of collagen and elastin. LOX family proteins are abundantly expressed in the remodeled heart of animals and humans and are implicated in cardiac fibrosis; however, their role in cardiac hypertrophy is unknown. In this study, in vitro stimulation with hypertrophic agonists significantly increased LOXL-1 expression, LOX enzyme activity and [ 3 H] leucine incorporation in neonatal rat cardiomyocytes. A LOX inhibitor, beta-aminopropionitrile (BAPN), inhibited agonist-induced leucine incorporation in cardiomyocytes in vitro, suggesting the involvement of LOXL-1 in cardiomyocyte hypertrophy. Abdominal aortic constriction in rats produced left ventricular hypertrophy in parallel with LOXL-1 mRNA upregulation. And BAPN administration significantly inhibited angiotensin II-induced cardiac hypertrophy in vivo. These results suggest a role of LOXL-1 in cardiac hypertrophy in vivo. We generated transgenic mice with cardiomyocyte-specific expression of LOXL-1. LOXL-1 transgenic mice pups were born normally and grew to adulthood without increased mortality; these mice exhibited a greater left ventricle to body weight ratio, larger myocyte diameter, and more brain natriuretic peptide expression than their wild-type littermates. Echocardiography revealed that the LOXL-1 transgenic mice also had greater wall thickness with preserved cardiac contraction. Our results indicate a possible fundamental role of LOXL-1 in cardiac hypertrophy.

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Lysyl oxidase: an oxidative enzyme and effector of cell function

Cited by 505 publications

References 82 publications

Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

New insights into elastic fiber assembly

Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice

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