Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury

Gotha, Lara; Lim, Sang Yup; Osherov, Azriel B.; Wolff, Rafael; Qiang, Beiping; Erlich, I.; Nili, Nafiseh; Pillarisetti, Sivaram; Chang, Ya Ting; Tran, Phan Kiet; Tryggvason, Karl; Hedin, Ulf; Tran‐Lundmark, Karin; Advani, Suzanne L.; Gilbert, Richard E.; Strauss, Bradley H.

doi:10.1152/ajpheart.00654.2013

Cited by 12 publications

(11 citation statements)

References 32 publications

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“…These mutant mice have impaired angiogenesis, delayed healing after experimental wounding and suppression of tumor growth [ 159 ]. When challenged with flow cessation of the carotid artery, the Hspg 2 Δ3/Δ3 mice show an enhanced intimal hyperplasia and smooth muscle cell proliferation [ 160 , 161 ]. Moreover, during mouse hind-limb ischemia, the HS chains of perlecan are key regulators of the angiogenic response [ 162 ].Collectively, these studies reaffirm the role of HS perlecan in modulating pro-angiogenic factors such as FGF2, VEGFA and PDGF.…”

Section: Pericellular and Basement Membrane Zone Proteoglycansmentioning

confidence: 99%

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

2015

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We provide a comprehensive classification of the proteoglycan gene families and respective protein cores. This updated nomenclature is based on three criteria: Cellular and subcellular location, overall gene/protein homology, and the utilization of specific protein modules within their respective protein cores. These three signatures were utilized to design four major classes of proteoglycans with distinct forms and functions: the intracellular, cell-surface, pericellular and extracellular proteoglycans. The proposed nomenclature encompasses forty-three distinct proteoglycan-encoding genes and many alternatively-spliced variants. The biological functions of these four proteoglycan families are critically assessed in development, cancer and angiogenesis, and in various acquired and genetic diseases where their expression is aberrant.

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Section: Pericellular and Basement Membrane Zone Proteoglycansmentioning

confidence: 99%

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

2015

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“…These two HSPG differ in regard to their localization: agrin was predominantly found in the subendothelial BM and perlecan was found in the BM underneath endothelial cells and around smooth muscle cells [4,206]. On the structural cells of the vessel wall, perlecan with its heparan sulfate chains may exert different functions, as it is reported to induce angiogenesis [207], yet to inhibit smooth muscle cell proliferation [208,209]. Additionally, PDGF-BB, one of the major factors driving vascular remodeling, contains a retention motif that allows binding to perlecan, thereby establishing a growth factor/morphogen gradient [210,211].…”

Section: Bm Hspgs In Phmentioning

confidence: 99%

Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?

Mutgan

Jandl

Kwapiszewska

2020

Cells

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Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.

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“…Given the importance of laminins for a number of cellular functions, this provides crucial data for future attempts to recreate the aortic valve through tissue engineering. The presence or absence of laminins, and other ECM components such as perlecan, [51][52][53][54] heparan sulfate, 16 and fibronectin 4,55 is bound to affect the viability of tissueengineered heart valve grafts, but other factors that influence graft viability also need to be considered. Aside from a lack of appropriate ECM components, structural deterioration of tissue-engineered heart valve grafts may be due to (i) immunogenicity, 56 (ii) thrombogenicity, 57 or (iii) incomplete or inappropriate valvular endothelial or interstitial cell repopulation.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold

Granath

Noren

Björck

et al. 2020

BioResearch Open Access

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Aortic valve stenosis is one of the most common cardiovascular diseases in western countries and can only be treated by replacement with a prosthetic valve. Tissue engineering is an emerging and promising treatment option, but in-depth knowledge about the microstructure of native heart valves is lacking, making the development of tissue-engineered heart valves challenging. Specifically, the basement membrane (BM) of heart valves remains incompletely characterized, and decellularization protocols that preserve BM components are necessary to advance the field. This study aims to characterize laminin isoforms expressed in healthy human aortic valves and establish a small animal decellularized aortic valve scaffold for future studies of the BM in tissue engineering. Laminin isoforms were assessed by immunohistochemistry with antibodies specific for individual α, β, and γ chains. The results indicated that LN-411, LN-421, LN-511, and LN-521 are expressed in human aortic valves ( n = 3), forming a continuous monolayer in the endothelial BM, whereas sparsely found in the interstitium. Similar results were seen in rat aortic valves ( n = 3). Retention of laminin and other BM components, concomitantly with effective removal of cells and residual DNA, was achieved through 3 h exposure to 1% sodium dodecyl sulfate and 30 min exposure to 1% Triton X-100, followed by nuclease processing in rat aortic valves ( n = 3). Our results provide crucial data on the microenvironment of valvular cells relevant for research in both tissue engineering and heart valve biology. We also describe a decellularized rat aortic valve scaffold useful for mechanistic studies on the role of the BM in heart valve regeneration.

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Heparan sulfate side chains have a critical role in the inhibitory effects of perlecan on vascular smooth muscle cell response to arterial injury

Cited by 12 publications

References 32 publications

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

Proteoglycan form and function: A comprehensive nomenclature of proteoglycans

Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?

Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold

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