Cyclic Nucleotide Hydrolysis in Bovine Aortic Endothelial Cells in Culture: Differential Regulation in Cobblestone and Spindle Phenotypes

Keravis, Thérèse; Komas, Narcisse; Lugnier, Claire

doi:10.1159/000025738

Cited by 29 publications

(24 citation statements)

References 55 publications

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“…Our data confirm the expression of PDE2, PDE3, PDE4, and PDE5 in bAECs and HUVECs (Lugnier and Schini, 1990;Ashikaga et al, 1997;Lugnier et al, 1999;Keravis et al, 2000, Miro et al, 2000Favot et al, 2003), unequivocally established that these enzymes are also expressed in HAECs and HMVECs, and demonstrate that PDEs were expressed to differing levels in these cells. Our data highlight potentially important differences between bovine and human aortic VECs as well as between the three human VECs studied.…”

Section: Discussionsupporting

confidence: 85%

“…In particular, bAECs were shown to express significant levels of PDE3B, an enzyme not expressed by any of the human VECs studied. Expression of PDE3B in bAECs is noteworthy because we have shown previously that PDE3B is an exclusively particulate enzyme (Liu and Maurice, 1998), a fact that perhaps accounts for the observation of Keravis et al (2000) that Ͼ60% of bAEC PDE3 activity was particulate. In addition, our data demonstrate clear vascular bed-based differences in the expression profile of PDEs in VECs.…”

Section: Discussionmentioning

confidence: 84%

“…In contrast, PDE5, PDE6, and PDE9 family enzymes selectively hydrolyze cGMP (Maurice et al, 2003). A limited number of studies have characterized PDE activities in VECs and shown that some bovine, rat, and human VECs contain activities consistent with expression of PDE1, PDE2, PDE3, PDE4, and PDE5 family enzymes (Lugnier and Schini, 1990;Ashikaga et al, 1997;Lugnier et al, 1999;Sadhu et al, 1999;Keravis et al, 2000;Miro et al, 2000;Thompson et al, 2002;Creighton et al, 2003;Favot et al, 2003;Maurice et al, 2003).…”

mentioning

confidence: 99%

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Vascular Endothelial Cell Cyclic Nucleotide Phosphodiesterases and Regulated Cell Migration: Implications in Angiogenesis

Netherton

Maurice²

2004

Mol Pharmacol

112

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Angiogenesis is necessary during embryonic development and wound healing but can be detrimental in pathologies, including cancer. Because initiation of angiogenesis involves migration and proliferation of vascular endothelial cells (VECs) and cAMPelevating agents inhibit these events, such agents may represent a novel therapeutic avenue to controlling angiogenesis. Intracellular cAMP levels are regulated by their synthesis by adenylyl cyclases and hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). In this report, we show that human VECs express variants of PDE2, PDE3, PDE4, and PDE5 families and demonstrate that the levels of these enzymes differ in VECs derived from aorta, umbilical vein, and microvascular structures. Selective inhibition of PDE2 did not increase cAMP in any VECs, whether in the absence or presence of forskolin, but it did inhibit migration of all VECs studied. Inhibition of PDE4 activity decreased migration, and in conjunction with forskolin, increased cAMP in all VECs studied. PDE3 inhibition potentiated forskolin-induced increases in cAMP and inhibited migration in VECs derived from aorta and umbilical vein but not in microvascular VECs. In experiments with combinations of PDE2, PDE3, and PDE4 inhibitors, a complex interaction between the abilities of these agents to limit human VEC migration was observed. Overall, our data are consistent with the hypothesis that PDE subtype inhibition allows different effects in distinct VEC populations and indicate that these agents may represent novel therapeutic agents to limit angiogenesis in complex human diseases.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 99%

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Vascular Endothelial Cell Cyclic Nucleotide Phosphodiesterases and Regulated Cell Migration: Implications in Angiogenesis

Netherton

Maurice²

2004

Mol Pharmacol

112

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“…More detailed analysis of the effects that are altered downstream from these enzymes may be necessary to further clarify this important issue. Although altered PDE expression in different endothelial phenotypes has also been reported (Keravis et al, 2000), the impact of these findings on our data remains to be established. PDE3A as a Therapeutic Target.…”

Section: Human Aortic Contractile and Synthetic Vsmc Express Differenmentioning

confidence: 70%

Reduced Phosphodiesterase 3 Activity and Phosphodiesterase 3A Level in Synthetic Vascular Smooth Muscle Cells: Implications for Use of Phosphodiesterase 3 Inhibitors in Cardiovascular Tissues

et al. 2002

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Vascular smooth muscle cells (VSMC) in situ function to control contraction and are said to express a contractile phenotype. However, during development or in response to vascular damage, VSMC proliferate and express a more synthetic phenotype. A survey of literature values for contractile and synthetic VSMC phosphodiesterase (PDE) 3 and PDE4 activities identified a marked difference in the PDE3 and PDE4 activities of these cells. In this study, a comparison of PDE3 and PDE4 activities in contractile and synthetic VSMC demonstrates that a reduced PDE3/PDE4 activity ratio in synthetic VSMC correlates with a reduced PDE3 activity and is associated with marked reductions in PDE3A mRNA and protein levels. Because we show that similar reductions in PDE3 activity and PDE3A levels occur upon culture of human aortic VSMC and that this phenomenon associates with the phenotypic switch that occurs to VSMC in response to vascular damage, our findings are presented in the context that PDE3 inhibition might be expected to selectively alter functions of contractile VSMC.

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“…In this context, recent studies of this phenomenon have concluded that these differences relate, at least in part, to authentic differences in the expression profile of PDE genes in the two distinct VSMC phenotypes (Rybalkin et al, 1997;Rybalkin and Bornfeldt, 1999;Dunkerley et al, 2002). Although many fewer studies have assessed PDE activities and expression in VEC (and in most instances only cultured synthetic/activated VEC were studied), the available literature identifies possible roles for PDE1, PDE2, PDE3, PDE4, and PDE5 family variants in these cells (Ashikaga et al, 1997;Zhao et al, 1997;Keravis et al, 2000;Thompson et al, 2002). Given the central role of VEC in processes such as blood vessel contractility, coagulation, inflammation, angiogenesis, and vascular remodelling, the therapeutic value of targeting VEC PDE will probably spur further analysis of PDE in these important cells.…”

Section: Pde Activity Expression and Targeting In Cells Of The Cardmentioning

confidence: 99%

Cyclic Nucleotide Phosphodiesterase Activity, Expression, and Targeting in Cells of the Cardiovascular System

Maurice¹,

Palmer²,

Tilley³

et al. 2003

Mol Pharmacol

291

255

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Cyclic AMP (cAMP) and cGMP regulate a myriad of cellular functions, such as metabolism, contractility, motility, and transcription in virtually all cell types, including those of the cardiovascular system. Considerable effort over the last 20 years has allowed identification of the cellular components involved in the synthesis of cyclic nucleotides, as well as effectors of cyclic nucleotide-mediated signaling. More recently, a central role for cyclic nucleotide phosphodiesterase (PDE) has also been elaborated in many cell types, including those involved in regulating the activities of the cardiovascular system. In this review, we introduce the PDE families whose members are expressed in cells of the cardiovascular system including cardiomyocytes, vascular smooth muscle cells, and vascular endothelial cells. Because cell behavior is a dynamic process influenced by numerous factors, we will attempt to emphasize how changes in the activity, expression, and targeting of PDE influence cyclic nucleotide-mediated regulation of the behavior of these cells.The cyclic nucleotides cAMP and cGMP regulate a myriad of cellular functions, including metabolism, contractility, motility, and transcription in virtually all cell types, including those of the cardiovascular system (Antoni, 2000;Klein, 2002). Although early work identified cAMP and cGMP as second messengers and led to the discovery of the proteins involved in coordinating the synthesis, degradation, and cellular actions of cyclic nucleotides, early models describing how these systems allowed cyclic nucleotide-mediated regulation of multiple cellular functions underestimated the levels of flexibility and specialization involved. In this context, recent work has identified large numbers of receptor (Marchese et al., 1999;Lucas et al., 2000), adenylyl cyclase (Hanoune and Defer, 2001), guanylyl cyclase (Garbers, 1999;Lucas et al., 2000), heterotrimeric G-protein (Marchese et al., 1999), and cyclic nucleotide phosphodiesterase (PDE) (Beavo and Reifsnyder, 1990;Beavo, 1995;Conti et al., 1995;Manganiello and Degerman, 1999;Conti, 2000;Conti and Jin, 2000;Houslay and Kolch, 2000;Soderling and Beavo, 2000;Francis et al., 2001;Houslay and Adams, 2003) protein families. Although many of the cellular effects of cAMP and cGMP are coordinated through their activation of cyclic nucleotide-dependent protein kinases (Lincoln et al., 1995), several other effectors are now known. Thus, cyclic nucleotidegated ion channels (Yau, 1994), cAMP-activated guanine nucleotide exchange factors (de Rooij et al., 1998;Kawasaki et al., 1998), and cyclic nucleotide PDEs have each been shown to transduce cyclic nucleotide-encoded information (Beavo and Reifsnyder, 1990;Beavo, 1995;Conti et al., 1995;Manganiello and Degerman, 1999;Conti, 2000;Conti and Jin, 2000;Houslay and Kolch, 2000;Soderling and Beavo, 2000;Francis et al., 2001;Houslay and Adams, 2003). More recently, an appreciation of the impact of regulated anchoring/targeting of cyclic nucleotide-regulated proteins to discrete subcell...

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Cyclic Nucleotide Hydrolysis in Bovine Aortic Endothelial Cells in Culture: Differential Regulation in Cobblestone and Spindle Phenotypes

Cited by 29 publications

References 55 publications

Vascular Endothelial Cell Cyclic Nucleotide Phosphodiesterases and Regulated Cell Migration: Implications in Angiogenesis

Vascular Endothelial Cell Cyclic Nucleotide Phosphodiesterases and Regulated Cell Migration: Implications in Angiogenesis

Reduced Phosphodiesterase 3 Activity and Phosphodiesterase 3A Level in Synthetic Vascular Smooth Muscle Cells: Implications for Use of Phosphodiesterase 3 Inhibitors in Cardiovascular Tissues

Cyclic Nucleotide Phosphodiesterase Activity, Expression, and Targeting in Cells of the Cardiovascular System

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