RGS2 is a primary terminator of β₂-adrenergic receptor-mediated G(i) signaling.

Two major β-adrenergic receptor (βAR) subtypes, β(1)AR and β(2)AR, are expressed in mammalian heart with β(1)AR coupling to G(s) and β(2)AR dually coupling to G(s) and G(i) proteins. In many types of chronic heart failure, myocardial contractile response to both β(1)AR and β(2)AR stimulation is severely impaired. The dysfunction of βAR signaling in failing hearts is largely attributable to an increase in G(i) signaling, because disruption of the G(i) signaling restores myocardial contractile response to β(1)AR as well as β(2)AR stimulation.

Design, generation, and testing of mammalian expression modules that tag membrane proteins.

The expression of mammalian membrane proteins in laboratory cell lines allows their biological functions to be characterized and carefully dissected. However, it is often difficult to design and generate effective antibodies for membrane proteins in the desired studies. As a result, expressed membrane proteins cannot be detected or characterized via common biochemical approaches such as western blotting, immunoprecipitation, or immunohistochemical analysis, and their cellular behaviors cannot be sufficiently investigated.

Stereochemistry of an agonist determines coupling preference of beta2-adrenoceptor to different G proteins in cardiomyocytes.

A fundamental question regarding receptor-G protein interaction is whether different agonists can lead a receptor to different intracellular signaling pathways. Our previous studies have demonstrated that although most beta(2)-adrenoceptor agonists activate both G(s) and G(i) proteins, fenoterol, a full agonist of beta(2)-adrenoceptor, selectively activates G(s) protein. Fenoterol contains two chiral centers and may exist as four stereoisomers.

Chemokine RANTES is upregulated in monocytes from patients with hyperhomocysteinemia.

Aim: To investigate the changes in plasma level of the chemokine RANTES (regulated upon activation, normal T cells expressed and secreted) and the responsiveness of lipopolysaccharide (LPS)-induced RANTES secretion from monocytes in patients with hyperhomocysteinemia (HHcy).

Methods: The plasma levels of homocysteine (Hcy), folate, and RANTES were measured in 38 control patients with normal Hcy levels and 40 patients with HHcy and the mRNA synthesis of RANTES in isolated human monocytes was determined by RNase protection assays.

Results: The plasma level of RANTES was elevated in HHcy patients compared with controls (median 5.

Endostatin binds biglycan and LDL and interferes with LDL retention to the subendothelial matrix during atherosclerosis.

Retention of lipoproteins to proteoglycans in the subendothelial matrix (SEM) is an early event in atherosclerosis. We recently reported that collagen XVIII and its proteolytically released fragment endostatin (ES) are differentially depleted in blood vessels affected by atherosclerosis. Loss of collagen XVIII/ES in atherosclerosis-prone mice enhanced plaque neovascularization and increased the vascular permeability to lipids by distinct mechanisms.

Folic acid reverses hyper-responsiveness of LPS-induced chemokine secretion from monocytes in patients with hyperhomocysteinemia.

Our previous study demonstrated that homocysteine (Hcy) mediated the expression and secretion of MCP-1 and IL-8 in human monocytes. In the present study, we investigated whether the responsiveness of isolated monocytes to lipopolysaccharide (LPS)-induced chemokine secretion was enhanced in patients with hyperhomocysteinemia (HHcy), and if so, whether this enhanced response could be inhibited by folic acid treatment. We studied 38 control subjects and 40 patients with HHcy.

Signal pathways underlying homocysteine-induced production of MCP-1 and IL-8 in cultured human whole blood.

Aim: To elucidate the mechanisms underlying homocysteine (Hcy)-induced chemokine production.

Methods: Human whole blood was pretreated with inhibitors of calmodulin (CaM), protein kinase C (PKC), protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK), and NF-kappaB and activators of PPARgamma for 60 min followed by incubation with Hcy 100 micromol/L for 32 h. The levels of mitogen chemokine protein (MCP)-1 and interleukin-8 (IL-8) were determined by enzyme-linked immunosorbant assay (ELISA).

Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood.

Aim: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood.

Methods: Human whole blood or different type of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP-1 and IL-8 level were measured by ELISA assay.

Loss of collagen XVIII enhances neovascularization and vascular permeability in atherosclerosis.

Background: Plaque neovascularization is thought to promote atherosclerosis; however, the mechanisms of its regulation are not understood. Collagen XVIII and its proteolytically released endostatin fragment are abundant proteoglycans in vascular basement membranes and the walls of major blood vessels. We hypothesized that collagen XVIII in the aortic wall inhibits the proliferation and intimal extension of vasa vasorum.

Homocysteine mediated expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human monocytes.

Homocysteine (Hcy) is an independent risk factor for cardiovascular disease. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) are major chemokines for leukocyte trafficking and have been identified in atheromatous plaques. MCP-1 and IL-8 have been found to express mainly by macrophages in human lesion.

Oxidant stress mechanism of homocysteine potentiating Con A-induced proliferation in murine splenic T lymphocytes.

Objective: An elevated plasma homocysteine (Hcy) level is considered an independent risk factor for atherosclerosis. However, the mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood. The effect of Hcy on T lymphocyte proliferation and its mechanisms were examined in normal and hyperhomocysteinemia ApoE-knockout mice.