Publications by authors named "Tai Xing Cui"

Article Synopsis
  • The study aimed to investigate how the protein hepcidin affects the stability of atherosclerotic plaques.
  • In experiments with mice lacking a specific protein, overexpression of hepcidin led to increased macrophage infiltration into plaques and reduced levels of collagen and smooth muscle cells, making the plaques less stable.
  • Hepcidin was found to enhance inflammation and oxidative stress in macrophages, particularly in the presence of oxidized low-density lipoprotein (ox-LDL), and contributed to the destabilization of atherosclerotic plaques through the retention of iron.
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Objective: We identified a ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene, which encodes a deubiquitinating enzyme and is expressed in the vasculature, by functional screening of a human endothelial cell (EC) cDNA library. UCHL1 is expressed in neurons, and abnormalities in UCHL1 are responsible for inherited Parkinson's disease via its effects on the ubiquitin-proteasome system. Therefore, the goal of present study was to clarify the role of the UCHL1 gene in vascular remodeling by evaluating nuclear factor-kappaB (NF-kappaB) inactivation in ECs and vascular smooth muscle cells (VSMCs).

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The detailed mechanism of the effects of extracellular Ca2+ entry blockade on angiotensin II (Ang II) type 1 (AT1) receptor-mediated growth-promoting signals in vascular smooth muscle cells (VSMCs) is not fully understood. Ang II stimulation caused biphasic activation of growth-promoting signals, reaching a peak at 5 to 10 min followed by a decrease and a second peak at around 2 to 4 h. Addition of PD98059 (2'-amino-3'-methoxyflavone), a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor, or AG490 [alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide], a Janus-activated kinase 2 (Jak2) inhibitor, even 4 h after Ang II treatment inhibited [3H]thymidine incorporation.

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We investigated the effects of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) on the inhibitory effects of an angiotensin II type-1 receptor (AT1) blocker on atherosclerosis and explored cellular mechanisms. We gave apolipoprotein E null mice a high-cholesterol diet for 10 weeks and measured atherosclerotic plaque area and lipid deposition. Neither 1 mg/kg per day of valsartan nor 3 mg/kg per day of fluvastatin had any effect on blood pressure or cholesterol concentration; however, both drugs decreased plaque area and lipid deposition after 10 weeks.

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Background: Activation of the renin-angiotensin system with increased levels of renin and angiotensin (Ang) II in pregnancy has been reported, but the vascular responsiveness to Ang II seems to be decreased, thereby keeping maternal blood pressure (BP) constant. We postulated that the balance of angiotensin type 1 (AT1) and angiotensin type 2 (AT2) receptor expression, which would exert antagonistic actions on vasoconstriction and cell growth, might control BP in pregnancy.

Methods: Using wild type (C57BL/6J), AT1a receptor null and AT2 receptor null mice, we examined the changes in BP, expression and localization of AT1 and AT2 receptors in placenta, umbilical cord, and uterus by immunohistochemical staining and urinary albumin measurement during pregnancy.

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Negative regulation of mitogenic pathways is a fundamental process that remains poorly characterized. The angiotensin II AT2 receptor is a rare example of a 7-transmembrane domain receptor that negatively cross-talks with receptor tyrosine kinases to inhibit cell growth. In the present study, we report the molecular cloning of a novel protein, ATIP1 (AT2-interacting protein), which interacts with the C-terminal tail of the AT2 receptor, but not with those of other receptors such as angiotensin AT1, bradykinin BK2, and adrenergic beta(2) receptor.

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Article Synopsis
  • Angiotensin II may play a role in insulin resistance, prompting a study on the effects of the AT1 receptor blocker valsartan in type 2 diabetic KK-Ay mice.
  • Valsartan, administered at a low dose, significantly improved insulin sensitivity by enhancing glucose uptake in skeletal muscle without affecting blood pressure.
  • It increased key signaling pathways related to insulin action, decreased inflammation, and boosted the translocation of GLUT4, ultimately improving glucose regulation in the mice.
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The present studies were undertaken to investigate the potential effect of a calcium channel blocker (CCB) to enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT1) receptor blocker (ARB) on vascular injury and the cellular mechanism of the effect of CCB on vascular remodeling. In polyethylene cuff-induced vascular injury of the mouse femoral artery, proliferation of vascular smooth muscle cells (VSMCs) and neointimal formation associated with activation of extracellular signal-regulated kinase (ERK), and tyrosine-phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3, inflammatory response assessed by monocyte chemoattractant protein-1 and tumor necrosis factor-alpha expression, as well as oxidative stress such as expression of NADH/NADPH oxidase p22(phox) subunit and superoxide production, were less in AT1a receptor null mice. Administration of nonhypotensive doses of a CCB, azelnidipine (0.

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In the present study we examined the effects of angiotensin II (Ang II) type 2 (AT(2)) receptor stimulation on AT(1) receptor-mediated monocyte chemoattractant protein-1 (MCP-1) expression and the possible mechanisms of AT(2) receptor-mediated signaling in cultured rat fetal vascular smooth muscle cells, which express both AT(1) and AT(2) receptors. Ang II stimulation induced MCP-1 mRNA expression as well as an increase in nuclear factor-kappaB (NF-kappaB) binding to the corresponding cis DNA element of the MCP-1 promoter region and a decrease in the cytosolic inhibitory protein-kappaB (IkappaB) protein level via AT(1) receptor stimulation, whereas stimulation of the AT(2) receptor decreased Ang II-induced MCP-1 expression, NF-kappaB DNA binding, and IkappaB degradation, suggesting that activation of the AT(2) receptor attenuated AT(1) receptor-mediated MCP-1 expression via a decrease in NF-kappaB DNA binding and an increase in IkappaB stability. Moreover, we demonstrated that AT(2) receptor stimulation attenuated TNFalpha-mediated NF-kappaB activation and MCP-1 expression.

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Objective: The pathogenetic mechanism of tobacco-related cardiovascular diseases is still not well defined. We examined the potential possibility of an interaction between nicotine, a major component of cigarette smoke, and angiotensin II (Ang II), which plays an important role in the pathogenesis of cardiovascular diseases characterized by Ang II type 1 (AT1) receptor-mediated abnormal growth of vascular smooth muscle cells (VSMC) and fibroblasts.

Methods And Results: Nicotine or Ang II-stimulated [3H]thymidine incorporation and c-fos expression in adult rat aortic VSMC and adventitial fibroblast.

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We examined the possibility of whether angiotensin (Ang) II type 1 (AT1) and type 2 (AT2) receptor stimulation differentially regulates collagen production in mouse skin fibroblasts. Both AT1 and AT2 receptors were expressed in neonatal skin fibroblasts prepared from wild-type mice to a similar degree, and the AT1a receptor was exclusively expressed as opposed to the AT1b receptor. In wild-type fibroblasts, Ang II increased collagen synthesis accompanied by an increase in expression of tissue inhibitor of metalloproteinase (TIMP)-1, and these increases were inhibited by valsartan, an AT1 receptor blocker, but augmented by PD123319, an AT2 receptor antagonist.

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Article Synopsis
  • The study investigates how imidapril, an ACE inhibitor, affects inflammatory vascular injury in mice lacking the AT1a receptor (AT1aKO) compared to normal mice (WT).
  • Results showed that imidapril reduced neointimal formation and the expression of inflammatory markers (MCP-1 and TNF-alpha) in both mouse types and increased cGMP levels.
  • The effectiveness of imidapril was diminished by blocking bradykinin receptors or inhibiting NO synthase, highlighting the importance of the bradykinin-NO system alongside angiotensin II suppression in vascular health.
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Background: The present studies were undertaken to investigate the potential effect of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) to enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT1) receptor blocker (ARB) on vascular neointimal formation and to explore the cellular mechanism of cross-talk of the AT1 receptor and statin in vascular smooth muscle cells (VSMCs).

Methods And Results: Neointimal formation and the proliferation of VSMCs induced by cuff placement around the femoral artery were significantly inhibited by treatment with an ARB, valsartan, at a dose of 0.1 mg x kg(-1) x d(-1) and with fluvastatin at a dose of 1 mg x kg(-1) x d(-1), which did not influence mean arterial blood pressure or plasma cholesterol level, whereas valsartan or fluvastatin alone at these doses did not affect neointimal formation or the proliferation of VSMCs.

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The effects of intracerebroventricular (ICV) injection of angiotensin II (ANG II) on blood pressure and water intake were examined with the use of ANG II receptor-deficient mice. ICV injection of ANG II increased systolic blood pressure in a dose-dependent manner in wild-type (WT) mice and ANG type 2 AT(2) receptor null (knockout) (AT(2)KO) mice; however, this increase was significantly greater in AT(2)KO mice than in WT mice. The pressor response to a central injection of ANG II in WT mice was inhibited by ICV preinjection of the selective AT(1) receptor blocker valsartan but exaggerated by the AT(2) receptor blocker PD-123319.

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The present study explored the possibility that estrogen may enhance the inhibitory effect of an angiotensin (Ang) II type 1 (AT1) receptor blocker on neointima formation in vascular injury, and investigated the signaling mechanism involved in their actions. Polyethylene cuff placement around the femoral artery of mice induced neointima formation and increased bromodeoxyuridine (BrdU) incorporation into vascular smooth muscle cells. These changes were significantly smaller in female mice than in male mice.

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Improvement of insulin resistance by ACE inhibitors has been suggested; however, this mechanism has not been proved. We postulated that activation of the bradykinin-nitric oxide (NO) system by an ACE inhibitor enhances glucose uptake in peripheral tissues by means of an increase in translocation of glucose transporter 4 (GLUT4), resulting in improvement of insulin resistance. Administration of an ACE inhibitor, temocapril, significantly decreased plasma glucose and insulin concentrations in type 2 diabetic mouse KK-Ay.

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Article Synopsis
  • The study reveals a novel interaction where the angiotensin II subtype 2 (AT2) receptor negatively affects the insulin receptor signaling pathways in PC12W cells, impacting key molecules like PI3K and Akt.
  • Stimulation of the AT2 receptor inhibits insulin's ability to activate the IRS-2 pathway without affecting IRS-1, leading to reduced Akt phosphorylation and blocking insulin's antiapoptotic effects.
  • The findings suggest that activation of SHP-1 by the AT2 receptor plays a crucial role in this inhibition, highlighting a potential mechanism for inducing apoptosis in these cells.
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Src homology 2-containing protein-tyrosine phosphatase 1 (SHP-1) is known to regulate signal transduction through the dephosphorylation of tyrosine kinases. In this study, we addressed the role of SHP-1 under tumor necrosis factor-alpha (TNF-alpha) stimulation in endothelial cells. The addition of recombinant vascular endothelial growth factor (50 ng/mL) or epidermal growth factor (50 ng/mL) significantly increased thymidine incorporation and c-fos promoter activity, whereas TNF-alpha (5 ng/mL) attenuated these effects in human or bovine aortic endothelial cells.

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Accumulating evidence suggests that estrogen exerts cardioprotective effects and protects against neointima formation in response to vascular injury in vivo, whereas angiotensin (Ang) II stimulation via the Ang II type 1 (AT(1)) receptor exaggerates vascular injury. We postulate that estrogen treatment antagonizes the AT(1) receptor-mediated growth-promoting effects in vascular smooth muscle cells (VSMCs). The present in vitro study was designed to explore this possibility and to establish the cellular mechanism whereby estrogen attenuates the growth of VSMCs.

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