A Genome-Based Resource for Molecular Cardiovascular Medicine

Hwang, David; Dempsey, Adam A.; Wang, Ruoxiang; Rezvani, Mojgan; Barrans, J. David; MHSc.,; Dai, Ken-Shwo; Wang, Huiyuan; Mā, Hong; Cukerman, Eva; Liu, Yuqing; Jianren, Gu; Zhang, Jinghui; Tsui, Stephen Kwok Wing; Waye, Mary Miu Yee; Fung, Kai-hung; Lee, Cheuk-Yu; Liew, Choong‐Chin

doi:10.1161/01.cir.96.12.4146

Cited by 160 publications

(112 citation statements)

References 59 publications

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“…During the course of random sequencing of cDNA clones from a human fetal heart cDNA library, we discovered several ESTs with significant sequence similarity to the APC gene (7,8). Our digital Northern analysis suggested a possible differential expression of APC during cardiovascular development and disease.…”

Section: Discussionmentioning

confidence: 99%

“…In our laboratory alone, we have generated over 50,000 ESTs from 11 cDNA libraries representing different cardiac developmental and diseased states. Sequence analysis of these ESTs from the libraries found several cDNA clones with significant sequence similarities to adenomatosis polyposis coli (APC) and its interacting protein, ␤-catenin (7,8). Further, computer-based digital Northern analysis of data from fetal, adult, and hypertrophic cDNA libraries suggested differential expressions of the aforementioned genes during cardiac development and disease.…”

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confidence: 99%

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Role of the Adenomatous Polyposis Coli Gene Product in Human Cardiac Development and Disease

Rezvani¹,

Liew

2000

Journal of Biological Chemistry

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Expressed sequence tag (EST) and digital Northern analyses of human fetal, adult, and hypertrophic heart cDNA libraries revealed ESTs with high homology to adenomatosis polyposis coli (APC) and its associated protein, ␤-catenin, as well as their differential expression. Thus, we hypothesize that the APC/␤-catenin pathway may play a role in cardiac development and disease. Reverse transcriptase-polymerase chain reaction analysis exhibited a higher APC expression in adult compared with fetal and hypertrophic heart but no significant difference in ␤-catenin mRNA level. However, ␤-catenin protein level was higher in fetal and hypertrophic heart compared with adult heart, suggesting the post-translational regulation of ␤-catenin by APC in the cardiovascular system. In vitro antisense inhibition of APC resulted a higher ␤-catenin protein expression leading to an incomplete myotube formation, suggesting APC/␤-catenin pathway involvement in myotube development. Western blot analysis further reveals three novel isoforms, APC-F, APC-A, and APC-D, ubiquitously expressed in fetal, adult, and hypertrophic heart, respectively. Isoform switching during development and disease pathogenesis suggests functionally distinct roles for each isoform. These data (i) demonstrate the usefulness of genome-based expression analysis for rapid discovery of differentially expressed genes, (ii) implicate the APC/␤-catenin pathway in the cardiovascular development, and (iii) demonstrate APC isoform switching during cardiac development and disease.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Role of the Adenomatous Polyposis Coli Gene Product in Human Cardiac Development and Disease

Rezvani¹,

Liew

2000

Journal of Biological Chemistry

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“…Almost half the abnormal transcripts could be classified as involved in signaling/communication or cell structure/ motility. 54 We identified 2 distinct groups of genes: 53 those associated with cell signaling and those associated with the mechanical regulation of vascular structure (cytoskeletal, cell membrane, extracellular matrix). Many studies have concentrated on the contribution of the extracellular matrix to arterial stiffness, but these data suggest that changes in the expression of signaling molecules plays an equally important role.…”

Section: Gene Expression Profilementioning

confidence: 99%

Structural and Genetic Bases of Arterial Stiffness

2005

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Abstract-Arterial stiffness has independent predictive value for cardiovascular events. We review data concerning the heritability of arterial stiffness, and propose an integrated view of the structural and genetic determinants of arterial stiffness, based on a candidate gene approach and recent studies on gene expression profile. Arterial stiffness seems to have a genetic component, which is largely independent of the influence of blood pressure and other cardiovascular risk factors. In animal models of essential hypertension (SHR and SHR-SP), structural modifications of the arterial wall include an increase in the number of elastin/smooth muscle cell (SMC) connections, and smaller fenestrations of the internal elastic lamina, possibly leading to redistribution of the mechanical load toward elastic materials. These modifications may give rise to mechanisms that explain why changes in arterial wall material accompanying wall hypertrophy in these animals are not associated with an increase in arterial stiffness. In monogenic connective tissue diseases (Marfan, Williams, and Ehlers-Danlos syndromes) and the corresponding animal models, precise characterization of the arterial phenotype makes it possible to determine the influence of abnormal genetically determined wall components on arterial stiffness. Such studies have highlighted the role of extracellular matrix signaling in the vascular wall and have shown that elastin and collagen not only display elasticity or rigidity but also are involved in the control of SMC function. These data provide strong evidence that arterial stiffness is affected by the amount and density of stiff wall material and the spatial organization of that material.

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“…We also utilized GeneSpring GX's "Post Hoc Test" program, which enables users to identify genes as common (or unique) from multiple datasets of differentially expressed genes, to produce a list of genes that were up-or down-regulated in the current experimental setting. For readers' reference, we partially applied gross, functional categorization (17) to the ontology information on individual genes showing significant expression changes in the Results section.…”

Section: Microarray Data Analysis and Statisticsmentioning

confidence: 99%