Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Connective tissue growth factor (CTGF) is a member of the recently described CCN gene family which contains CTGF itself, cyr61, nov, elm1, Cop1, and WISP-3. CTGF is transcriptionally activated by several factors although its stimulation by transforming growth factor beta (TGF-beta) has attracted considerable attention. CTGF acts to promote fibroblast proliferation, migration, adhesion, and extracellular matrix formation, and its overproduction is proposed to play a major role in pathways that lead to fibrosis, especially those that are TGF-beta-dependent. This includes fibrosis of major organs, fibroproliferative diseases, and scarring. CTGF also appears to play a role in the extracellular matrix remodeling that occurs in normal physiological processes such as embryogenesis, implantation, and wound healing. However, recent advances have shown that CTGF is involved in diverse autocrine or paracrine actions in several other cell types such as vascular endothelial cells, epithelial cells, neuronal cells, vascular smooth muscle cells, and cells of supportive skeletal tissues. Moreover, in some circumstances CTGF has negative effects on cell growth in that it can be antimitotic and apoptotic. In light of these discoveries, CTGF has been implicated in a diverse variety of processes that include neovascularization, transdifferentiation, neuronal scarring, atherosclerosis, cartilage differentiation, and endochondral ossification. CTGF has thus emerged as a potential important effector molecule in both physiological and pathological processes and has provided a new target for therapeutic intervention in fibrotic diseases.
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PMID:Connective tissue growth factor: what's in a name? 1100 22

CYR61 (CCN1) is an extracellular matrix-associated protein of the CCN family, which also includes CTGF (CCN2), NOV (CCN3), WISP-1 (CCN4), WISP-2 (CCN5), and WISP-3 (CCN6). Purified CYR61 induces neovascularization in corneal implants, and Cyr61-null mice suffer embryonic death due to vascular defects, thus establishing that CYR61 is an important regulator of angiogenesis. Aberrant expression of Cyr61 is associated with breast cancer, wound healing, and vascular diseases such as atherosclerosis and restenosis. In culture, CYR61 functions through integrin-mediated pathways to promote cell adhesion, migration, and proliferation. Here we show that CYR61 can also promote cell survival and tubule formation in human umbilical vein endothelial cells. Furthermore, we have dissected the integrin receptor requirements of CYR61 with respect to its pro-angiogenic activities. Thus, CYR61-induced cell adhesion and tubule formation occur through interaction with integrin alpha(6)beta(1) in early passage endothelial cells in which integrins have not been activated. By contrast, in endothelial cells in which integrins are activated by phorbol ester or vascular endothelial growth factor, CYR61-promoted cell adhesion, migration, survival, growth factor-induced mitogenesis, and endothelial tubule formation are all mediated through integrin alpha(v)beta(3). These findings indicate that CYR61 is an activation-dependent ligand of integrin alpha(v)beta(3) and an activation-independent ligand of integrin alpha(6)beta(1) and that these integrins differentially mediate the pro-angiogenic activities of CYR61. These findings help to define the mechanisms by which CYR61 acts as an angiogenic regulator, provide a molecular interpretation for the loss of vascular integrity and increased apoptosis of vascular cells in Cyr61-null mice, and underscore the importance of CYR61 in the development and homeostasis of the vascular system.
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PMID:Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3 and alpha6beta1 in human umbilical vein endothelial cells. 1236 23

CYR61 (CCN1) is a member of the CCN family of secreted matricellular proteins that includes connective tissue growth factor (CCN2), NOV (CCN3), WISP-1 (CCN4), WISP-2 (CCN5), and WISP-3 (CCN6). First identified as the product of a growth factor-inducible immediate-early gene, CYR61 is an extracellular matrix-associated angiogenic inducer that functions as a ligand of integrin receptors to promote cell adhesion, migration, and proliferation. Aberrant expression of Cyr61 is associated with breast cancer, wound healing, and vascular diseases such as atherosclerosis and restenosis. To understand the functions of CYR61 during development, we have disrupted the Cyr61 gene in mice. We show here that Cyr61-null mice suffer embryonic death: approximately 30% succumbed to a failure in chorioallantoic fusion, and the reminder perished due to placental vascular insufficiency and compromised vessel integrity. These findings establish CYR61 as a novel and essential regulator of vascular development. CYR61 deficiency results in a specific defect in vessel bifurcation (nonsprouting angiogenesis) at the chorioallantoic junction, leading to an undervascularization of the placenta without affecting differentiation of the labyrinthine syncytiotrophoblasts. This unique phenotype is correlated with impaired Vegf-C expression in the allantoic mesoderm, suggesting that CYR61-regulated expression of Vegf-C plays a role in vessel bifurcation. The genetic and molecular basis of vessel bifurcation is presently unknown, and these findings provide new insight into this aspect of angiogenesis.
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PMID:CYR61 (CCN1) is essential for placental development and vascular integrity. 1244 88