Cell migration in response to the amino-terminal fragment of urokinase requires epidermal growth factor receptor activation through an ADAM-mediated mechanism.

Background: Cell migration is an integral component of intimal hyperplasia development and proteases are pivotal in the process. Understanding the role of urokinase signaling within the cells of vasculature remains poorly defined. The study examines the role of amino-terminal fragment (ATF) of urokinase on a pivotal cross-talk receptor, epidermal growth factor receptor (EGFR).

Mechanisms of sphingosine-1-phosphate-induced akt-dependent smooth muscle cell migration.

Background: Sphingosine-1-phosphate (S-1-P) is a bioactive sphingolipid released from activated platelets that stimulates migration of vascular smooth muscle cells (VSMC) in vitro. S-1-P will activate akt, which can regulate multiple cellular functions including cell migration. Akt activation is downstream of phosphatidylinositol 3'-kinase (PI3-K) and phosphoinositide-dependent protein kinase-1 (PDK1).

Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent.

Background: With the rise in metabolic syndrome, understanding the role of insulin signaling within the cells of vasculature has become more important but yet remains poorly defined. This study examines the role of insulin actions on a pivotal cross-talk receptor, epidermal growth factor receptor (EGFR). EGFR is transactivated by both G-protein-coupled receptors and receptor-linked tyrosine kinases and is key to many of their responses.

Sphingosine-1-phosphate-induced oxygen free radical generation in smooth muscle cell migration requires Galpha12/13 protein-mediated phospholipase C activation.

Background: Sphingosine-1-phosphate (S-1-P) is a bioactive sphingolipid that stimulates the migration of vascular smooth muscle cell (VSMC) through G-protein coupled receptors; it has been shown to activate reduced nicotinamide dinucleotide phosphate hydrogen (NAD[P]H) oxidase. The role of phospholipase C (PLC) in oxygen free radical generation, and the regulation of VSMC migration in response to S-1-P, are poorly understood.

Methods: Rat arterial VSMC were cultured in vitro.

Patterns of kinase activation induced by injury in the murine femoral artery.

Background: Intimal hyperplasia remains the principal lesion in the development of restenosis after vessel wall injury. Cell signaling in vascular smooth muscle cells remains a potential molecular target to modulate the development of intimal hyperplasia. The aim of this study was to define a baseline pattern of histological changes and kinase activation in a murine model.

Mechanisms of kringle fragment of urokinase-induced vascular smooth muscle cell migration.

Background: Urokinase plasminogen activator (uPA) is involved in vessel remodeling and mediates smooth muscle cell migration. Migration in response to uPA is dependent on both the growth factor binding domain at the aminoterminal end and the kringle (K) domain of the molecule. uPA is readily degraded in vivo into these constitutive domains.

Plasminogen activator system and vascular disease.

Vascular diseases, such as atherosclerosis, thromboembolic disorders and stroke, in addition to surgical procedures such as restenosis, all share the plasminogen activator system as a central component in the pathogenesis of vascular injury. Since the development of plasminogen deficient mice our knowledge of the effects of this proteolytic system in cardiovascular disease has vastly increased. The plasminogen activator system plays a key role in vascular homeostasis and constitutes a critical response mechanism to cardiovascular injury.

Plasmin-induced smooth muscle cell proliferation requires epidermal growth factor activation through an extracellular pathway.

Background: Plasminogen activators are used routinely for thrombolysis. They lead to the generation of the protease, plasmin, which can induce smooth muscle cell proliferation and may thus promote further intimal hyperplasia in the thrombolysed vessel. We have shown recently that plasmin induces extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated cell proliferation.

Urokinase-induced smooth muscle cell migration requires PI3-K and Akt activation.

Objective: To examine the role of the phospho-inositol-3'-kinase (PI3-K)-akt signaling axis during smooth muscle cell (SMC) migration in response to the aminoterminal fragment of urokinase (ATF).

Background: Urokinase (uPA) is involved in vessel remodeling and mediates smooth muscle cell migration. Migration in response to urokinase is dependent on ATF.

Urokinase-induced smooth muscle cell responses require distinct signaling pathways: a role for the epidermal growth factor receptor.

Objective: Urokinase plasminogen activator (uPA) a key serine protease during remodeling, is capable of inducing both smooth muscle cell migration and proliferation. However, the signals that produce these responses are poorly understood.

Methods: Early passage rat aortic arterial smooth muscle cells were cultured in vitro and standard assays of DNA synthesis ([ 3 H]thymidine incorporation), cell proliferation (manual cell counting), and migration (linear wound assay and Boyden chamber) were used to study the cells responses to uPA.

Plasmin induces smooth muscle cell proliferation.

Background: Plasminogen activators are routinely used for thrombolysis. They lead to the generation of the protease, plasmin, which can induce smooth muscle cell proliferation and may thus promote further intimal hyperplasia in the thrombolysed vessel. The signaling pathways used by plasmin are not understood.

Sphingosine-1-phosphate-induced smooth muscle cell migration involves the mammalian target of rapamycin.

Background: Vascular smooth muscle cell (SMC) migration is an important component of the development of intimal hyperplasia. Sphingosine-1-phosphate (S-1-P) is a lipid released from activated platelets with numerous cellular effects including the stimulation of SMC migration in vitro. We examined the role of the mammalian target of rapamycin and ribosomal p70S6 kinase (p70S6K) in S-1-P-induced SMC migration .

Differential regulation of ERK1/2 and p38(MAPK) by components of the Rho signaling pathway during sphingosine-1-phosphate-induced smooth muscle cell migration.

Objective: To determine the role of rhosignaling in sphingosine-1-phosphate (S-1-P)-induced smooth muscle cell migration.

Background: S-1-P is a bioactive sphingolipid released from activated platelets stimulating migration of smooth muscle cells (SMC) in vitro through Galphai G-proteins and MAPK activation. Rho is one of the key small GTPases required for cytoskeletal reorganization and MAPK activation during migration.

Plasminogen activator inhibitor-1 deficiency enhances flow-induced smooth muscle cell migration.

Introduction: We determined the role of smooth muscle cell (SMC)-derived plasminogen activator inhibitor-1 (PAI-1) in the flow-induced SMC migratory response.

Materials And Methods: Wild type (wt) or PAI-1 knockout SMC were cultured in the absence or presence of endothelial cells (EC) under static or pulsatile flow conditions in a perfused culture system. SMC migration was then assessed by Transwell assay.

Neuropeptide Y Y(1) receptor regulates protein turnover and constitutive gene expression in hypertrophying cardiomyocytes.

Increased levels of neuropeptide Y correlate with severity of left ventricular hypertrophy in vivo. At cardiomyocyte level, hypertrophy is characterised by increased mass and altered phenotype. The aims were to determine the contributions of increased synthesis and reduced degradation of protein to neuropeptide Y-mediated increase in mass, assess effects on gene expression, and characterise neuropeptide Y Y receptor subtype involvement.