Low density lipoproteins downregulate lysyl oxidase in vascular endothelial cells and the arterial wall

Rodrı́guez, Carmen; Raposo, Berta; Martı́nez-González, José; Casaní, Laura; Badimon, Lina

doi:10.1016/s0214-9168(04)78956-1

Cited by 24 publications

(37 citation statements)

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“…48 Exogenous lipids supplied for more than a week results in a doubling of cholesterol levels, 48 which downregulates elastin maturation (by inhibiting lysyloxidase activity required for cross-linking) 49 and induces early vascular lipid damage in a critical developmental period of the still immature vessels. Of particular note, these effects are most prominent in the abdominal aorta prone to lipid accumulation, 50 which is an appealing explanation for prematurity's preferential effects on the abdominal aortic section in our study.…”

Section: Discussionmentioning

confidence: 99%

Aortic Elastic Properties in Preschool Children Born Preterm

Komazec

Posod

Schwienbacher

et al. 2016

ATVB

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Objective-Preterm birth predisposes children to the development of cardiovascular diseases in adulthood. The aim of this study was to characterize elastic properties of the aorta at preschool age and test the hypothesis that prematurity is associated with decreased aortic distensibility and increased stiffness, both of which are predictors of increased cardiovascular risk. Approach and Results-In an observational study of 76 five-to seven-year-old children born at a gestational age <32 weeks and 79 term-born controls, elastic parameters of the ascending and descending abdominal aorta were determined noninvasively by means of M mode echocardiographic tracings and calculated using computerized wall contour analysis. Compared with children born at term, the preterm group showed significantly reduced distensibility and increased stiffness of the descending abdominal aorta. These results remained significant under multivariable adjustment for birth weight z score, maternal smoking in pregnancy, maternal education, family history of cardiovascular disease, breastfeeding, childhood nutrition, and current body mass index z score (multivariable odds ratios and 95% confidence intervals 5.1, 1.7-15.9; P=0.005 and 2.8, 1.0-7.9; P=0.046, respectively). Further adjustment for intravenous lipid therapy attenuated the strength of association. Elastic properties of the ascending aorta did not differ between the 2 study groups. Conclusions-Children

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Section: Discussionmentioning

confidence: 99%

Aortic Elastic Properties in Preschool Children Born Preterm

Komazec

Posod

Schwienbacher

et al. 2016

ATVB

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“…However, lysyl oxidase was not detectable at the transcriptional level in WT and IL-6 Ϫ/Ϫ mice, because we analyzed only adult animals that showed no special vessel development or atherosclerosis. Moreover, hypercholesterolemia, as observed in ApoE Ϫ/Ϫ -IL-6 Ϫ/Ϫ mice, downregulates lysyl oxidase 34 and subsequently may contribute to lesion formation. Thus, alteration of extracellular matrix assembly, which was observed in the present study, may represent a vascular developmental defect that is induced by a lifetime deficiency of IL-6.…”

Section: Schieffer Et Al Interleukin-6 In Experimental Atherosclerosimentioning

confidence: 99%

Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis

Schieffer

Selle²,

Hilfiker³

et al. 2004

Circulation

289

189

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Background— Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis. Methods and Results— To assess the role of IL-6 in atherosclerosis, ApoE −/− – IL-6 −/− double-knockout mice were generated, fed a normal chow diet, and housed for 53±4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE −/− – IL-6 −/− mice compared with ApoE −/− , wild-type (WT), and IL-6 −/− mice. Plaques of ApoE −/− – IL-6 −/− mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase-polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE −/− – IL-6 −/− mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced. Conclusions— Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoE K −/− – IL-6 −/− mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.

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“…40,41 On the other hand, atherogenic concentrations of low-density lipoprotein and tumor necrosis factor α reduce LOX mRNA. 42,43 Song et al 44 have also shown that interferon-γ inhibits LOX gene expression through binding to the antagonistic transcriptional factor, interferon regulatory factor 2, in vascular SMCs.In contrast to our understanding of these transcriptional regulations of LOX, little is known regarding LOX protein metabolism. In the present study, we demonstrated for the first time that the PGE 2 -EP4 signal promoted lysosomal degradation of LOX protein.…”

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confidence: 99%

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

et al. 2014

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E lastic fibers are the largest structures in the extracellular matrix. Beginning with the onset of pulsatile blood flow in the developing aorta and pulmonary artery, smooth muscle cells (SMCs) in the vessel wall produce a complex extracellular matrix that ultimately defines the mechanical properties that are critical for proper function of the neonatal and adult vascular system. 1 As such, hemodynamics and mechanical stress are considered to be the main regulators in the formation of the vascular elastic fiber system during development. 2 Clinical Perspective on p 496The ductus arteriosus (DA) and its connecting elastic arteries (ie, the descending aorta and the main pulmonary trunk) are exposed to essentially the same mechanical forces and hemodynamics. However, since 1914, it has been widely recognized in multiple species that the DA exhibits sparse elastic fibers in the middle layer compared with adjacent elastic arteries, as well as disassembly and fragmentation of the internal elastic lamina. [3][4][5][6][7][8] In the human fetal aorta, newly synthesized uncrosslinked elastin appears at 23 weeks of gestational age to be unevenly distributed on the surface of microfibrils, where it forms continuous strips of variable width. 9 However, the DA exhibits fewer elastic fibers than the aorta. 4,6 This decreased elastogenesis is the hallmark of the vascular remodeling of the DA in humans and a variety of other species. [3][4][5][6][7] It has been suggested that this muscular phenotype of the DA allows it to collapse easily at birth when prostaglandin E 2 (PGE 2 ) is withdrawn and blood flow between the aorta and the pulmonary artery is reduced, thereby permitting immediate postnatal closure of the DA. Conversely, it is known that abnormalities of elastic fibers and elastic lamina are primarily responsible for the persistence of the DA in some human cases.10,11 These abnormalities likely prevent intimal cushion formation and make it difficult to collapse the arterial wall. Therefore, it is Background-Elastic fiber formation begins in mid-gestation and increases dramatically during the last trimester in the great arteries, providing elasticity and thus preventing vascular wall structure collapse. However, the ductus arteriosus (DA), a fetal bypass artery between the aorta and pulmonary artery, exhibits lower levels of elastic fiber formation, which promotes vascular collapse and subsequent closure of the DA after birth. The molecular mechanisms for this inhibited elastogenesis in the DA, which is necessary for the establishment of adult circulation, remain largely unknown. Methods and Results-Stimulation of the prostaglandin E 2 (PGE 2 ) receptor EP4 significantly inhibited elastogenesis and decreased lysyl oxidase (LOX) protein, which catalyzes elastin cross-links in DA smooth muscle cells (SMCs), but not in aortic SMCs. Aortic SMCs expressed much less EP4 than DASMCs. Adenovirus-mediated overexpression of LOX restored the EP4-mediated inhibition of elastogenesis in DASMCs. In EP4-knockout mice, electron microscopi...

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Low density lipoproteins downregulate lysyl oxidase in vascular endothelial cells and the arterial wall

Cited by 24 publications

References 0 publications

Aortic Elastic Properties in Preschool Children Born Preterm

Aortic Elastic Properties in Preschool Children Born Preterm

Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis

Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

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Low density lipoproteins downregulate lysyl oxidase in vascular endothelial cells and the arterial wall

Cited by 24 publications

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Aortic Elastic Properties in Preschool Children Born Preterm

Aortic Elastic Properties in Preschool Children Born Preterm

Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis

Prostaglandin E 2 Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling

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Product

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Prostaglandin E ₂ Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling