Genetic variability in the extracellular matrix as a determinant of cardiovascular risk: association of type III collagen COL3A1 polymorphisms with coronary artery disease

Muckian, Clare; Fitzgerald, Anthony P.; O’Neill, Anne; O'Byrne, Anna; Fitzgerald, Desmond J.; Shields, Denis C.

doi:10.1182/blood-2002-01-0283

Cited by 21 publications

(17 citation statements)

References 21 publications

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“…One example was the Col3a1 gene, which encodes collagen III that is expressed in blood vessels and appears together with collagen I in thickened intima of atherosclerotic lesions and most likely contributes to plaque growth and narrowing of arterial lumen (35). Another notable down-regulated gene was the Svil gene, the encoded protein of which, supervillin, is an F-actin-binding protein implicated in migration, adhesion, and signal transduction to the cell nucleus (36).…”

Section: Table II Genes Regulated By Ha12 In Brain Capillary Endothelmentioning

confidence: 99%

Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner

Takahashi

Kamiryo

et al. 2005

Journal of Biological Chemistry

120

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Hyaluronan is a glycosaminoglycan of the extracellular matrix. In tumors and during chronic inflammatory diseases, hyaluronan is degraded to smaller fragments, which are known to stimulate endothelial cell differentiation. In this study, we have compared the molecular mechanisms through which hyaluronan dodecasaccharides (HA12), and the known angiogenic factor, fibroblast growth factor 2 (FGF-2), induce capillary endothelial cell sprouting in a three-dimensional collagen gel. The gene expression profiles of unstimulated and HA12-or FGF-2-stimulated endothelial cells were compared using a microarray analysis approach. The data revealed that both FGF-2 and HA12 promoted endothelial cell morphogenesis in a process depending on the expression of ornithine decarboxylase (Odc) and ornithine decarboxylase antizyme inhibitor (Oazi) genes. Among the genes selectively up-regulated in response to HA12 was the chemokine CXCL1/GRO1 gene. The notion that the induction of CXCL1/GRO1 is of importance for HA12-induced endothelial cell sprouting was supported by the fact that morphogenesis was inhibited by antibodies specifically neutralizing the CXCL1/GRO1 protein product. HA12-stimulated endothelial cell differentiation was exerted via binding to CD44 since it was inhibited by antibodies blocking CD44 function. Our data show that hyaluronan fragments and FGF-2 affect endothelial cell morphogenesis by the induction of overlapping but also by distinct sets of genes.

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Section: Table II Genes Regulated By Ha12 In Brain Capillary Endothelmentioning

confidence: 99%

Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner

Takahashi

Kamiryo

et al. 2005

Journal of Biological Chemistry

120

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“…Forty-five of these genes have been implicated previously in CVD (24 genes) [24][25][26] and T2D (21 genes). 14,27,28 Five of the 8 commonly enriched pathways, namely, HCM, dilated cardiomyopathy, ARVC, focal adhesion, and extracellular matrix-receptor interaction signaling, were also found to be highly interconnected as demonstrated by a shared common set of 117 genes among them ( Figure 1). Besides the shared pathways across diseases and ethnicities, we also identified disease-and ethnicity-specific pathways (Table VIII in the Data Supplement).…”

Section: Identification Of Biological Pathways Using Integrative Pathmentioning

confidence: 99%

Shared Molecular Pathways and Gene Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in Women Across Diverse Ethnicities

Chan

Huang

Meng

et al. 2014

Circ Cardiovasc Genet

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It has long been known that cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors and pathophysiological intermediaries including obesity, dyslipidemia, insulin resistance, and proinflammatory and prothrombotic states. [1][2][3] However, the key molecular drivers underlying these highly correlated phenotypes as well as the potential regulatory networks shared in the pathogenesis of CVD and T2D remain poorly understood. Clinical Perspective on p 919Of the ≈60 genetic loci identified for CVD and T2D in large-scale genome-wide association studies (GWAS), 5 only 2 significant loci (TCF7L2 and VEGFA) are shared between the 2 diseases. There are ≥3 fundamentally important questions that remain to be answered. First, are there additional genetic risks, either alone or concentrated in specific regulatory networks that may explain the pathophysiological connections between CVD and T2D? Second, are there any ethnicityspecific genetic mechanisms for these 2 common vascular diseases, given that there are drastic ethnicity-specific differences in their risk and linkage disequilibrium patterns. [6][7][8] Third, although common genetic loci have been detected across different populations (eg, the Chr9p21 locus for CVD and the TCF7L2 locus for T2D) supporting the presence of common pathological paths across ethnicity, to what degree molecular mechanisms are shared across ethnicities?To answer these 3 questions, we performed 2 GWAS for both CVD and T2D using an integrative pathway and network analysis in the national Women's Health Initiative SNP Health Association Resource (WHI-SHARe) and the Genomics and Background-Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these 2 disorders remain unknown. Methods and Results-Using an integrative pathway and network analysis, we performed genome-wide association studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women who participated in the national Women's Health Initiative single-nucleotide polymorphism (SNP) Health Association Resource and the Genomics and Randomized Trials Network. Eight top pathways and gene networks related to cardiomyopathy, calcium signaling, axon guidance, cell adhesion, and extracellular matrix seemed to be commonly shared between CVD and T2D across all 3 ethnic groups. We also identified ethnicity-specific pathways, such as cell cycle (specific for Hispanic American and Caucasian American) and tight junction (CVD and combined CVD and T2D in Hispanic American). In network analysis of gene-gene or protein-protein interactions, we identified key drivers that included COL1A1, COL3A1, and ELN in the shared pathways for both CVD and T2D. These key driver genes were cross-validated in multiple mouse models of diabetes mellitus and atherosclerosis. Conclusions-Our integrative analysis of American women of 3 ethnicities identified multiple shared biological pathways and key regulatory ge...

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“…This includes genetic studies (6)(7)(8)(9)(10). In spite of this extensive research, a practical and reliable index of platelet activation has not been found.…”

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confidence: 98%

Platelets as Predictors of Vascular Risk: Is There a Practical Index of Platelet Activity?

Tsiara¹,

Elisaf

Jagroop

et al. 2003

Clin Appl Thromb Hemost

296

256

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Activated platelets play a role in the pathogenesis of coronary heart disease (CHD). Following activation, platelets change shape, aggregate, and release several bioactive substances. The aim of this review is to identify if there is a simple and cost-effective method that indicates platelet activation and predicts the risk of CHD and vascular events. The rationale for identifying high-risk patients is to reduce their risk of vascular events by administering appropriate and effective antiplatelet treatment, like aspirin, clopidogrel, or combination regimens. Many laboratory tests estimating platelet activity have been described. Some are relatively simple, such as spontaneous or agonist-induced platelet aggregation. Other tests include measuring the mean platelet volume (MPV) or plasma soluble P-selectin levels. Some more complex tests include flow cytometry to determine platelet GP IIb/IIIa receptors, platelet surface P-selectin, platelet-monocyte aggregates, and microparticles. Only few prospective studies assessed the predictive value of platelet activation in healthy individuals. Although the MPV seems an 'easy' method, there are insufficient data supporting its ability to predict the risk of a vascular event in healthy adults. Platelet aggregation, in whole blood or in platelet-rich plasma was not consistently predictive of vascular risk. Soluble P-selectin measurement is a promising method but it needs further evaluation. Flow cytometry methods are costly, time-consuming, and need specialized equipment. Thus, they are unlikely to be useful in estimating the risk in large numbers of patients. There is as yet no ideal test for the detection of platelet activation. Each currently available test has merits and disadvantages. Simple methods such as the MPV and the determination of platelet release products need further evaluation.

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Genetic variability in the extracellular matrix as a determinant of cardiovascular risk: association of type III collagen COL3A1 polymorphisms with coronary artery disease

Cited by 21 publications

References 21 publications

Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner

Hyaluronan Fragments Induce Endothelial Cell Differentiation in a CD44- and CXCL1/GRO1-dependent Manner

Shared Molecular Pathways and Gene Networks for Cardiovascular Disease and Type 2 Diabetes Mellitus in Women Across Diverse Ethnicities

Platelets as Predictors of Vascular Risk: Is There a Practical Index of Platelet Activity?

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