Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice.

Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice.

Tumor suppressor protein p53 negatively regulates ischemia-induced angiogenesis and arteriogenesis.

Objective: The tumor suppressor protein p53 regulates angiogenesis and is a key regulatory mediator of cellular apoptosis, proliferation, and growth. p53 expression is induced in response to ischemia; however, its role in regulating ischemia-induced angiogenesis and arteriogenesis remains undefined. The objective of this study was to define the role of p53 in regulating ischemia-induced angiogenesis and arteriogenesis and to identify mechanisms by which this regulation occurs in vivo.

Matrix Metalloproteinase 9 (MMP-9) Regulates Vein Wall Biomechanics in Murine Thrombus Resolution.

Objective: Deep venous thrombosis is a common vascular problem with long-term complications including post-thrombotic syndrome. Post-thrombotic syndrome consists of leg pain, swelling and ulceration that is related to incomplete or maladaptive resolution of the venous thrombus as well as loss of compliance of the vein wall. We examine the role of metalloproteinase-9 (MMP-9), a gene important in extracellular remodeling in other vascular diseases, in mediating thrombus resolution and biomechanical changes of the vein wall.

Recanalization and flow regulate venous thrombus resolution and matrix metalloproteinase expression in vivo.

Objective: We examined the role of thrombus recanalization and ongoing blood flow in the process of thrombus resolution by comparing two murine in vivo models of deep venous thrombosis.

Methods: In CD1 mice, we performed surgical inferior vena cava ligation (stasis thrombosis), stenosis (thrombosis with recanalization), or sham procedure. We analyzed thrombus weight over time as a measure of thrombus resolution and quantified the messenger RNA and protein levels of membrane-type matrix metalloproteinases (MT-MMPs) as well as effectors of the plasmin complex at days 4, 8, and 12 after surgery.

Enhanced venous thrombus resolution in plasminogen activator inhibitor type-2 deficient mice.

Background: The resolution of deep vein thrombosis requires an inflammatory response and mobilization of proteases, such as urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), to degrade the thrombus and remodel the injured vein wall. Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor (serpin) with unique immunosuppressive and cell survival properties that was originally identified as an inhibitor of uPA.

Objective: To investigate the role of PAI-2 in venous thrombus formation and resolution.

Activated protein C accelerates venous thrombus resolution through heme oxygenase-1 induction.

Background: Thrombus resolution is a complex process that involves thrombosis, leukocyte-mediated thrombolysis, and the final resolution of inflammation. Activated protein C (APC) is an anticoagulant that also possesses immunoregulatory activities.

Aim: In this study, we sought to examine the effects of APC administration on thrombus resolution using a mouse model of deep vein thrombosis by ligating the inferior vena cava (IVC).

A phylogenomic profile of hemerythrins, the nonheme diiron binding respiratory proteins.

Background: Hemerythrins, are the non-heme, diiron binding respiratory proteins of brachiopods, priapulids and sipunculans; they are also found in annelids and bacteria, where their functions have not been fully elucidated.

Results: A search for putative Hrs in the genomes of 43 archaea, 444 bacteria and 135 eukaryotes, revealed their presence in 3 archaea, 118 bacteria, several fungi, one apicomplexan, a heterolobosan, a cnidarian and several annelids. About a fourth of the Hr sequences were identified as N- or C-terminal domains of chimeric, chemotactic gene regulators.

Globin gene family evolution and functional diversification in annelids.

Globins are the most common type of oxygen-binding protein in annelids. In this paper, we show that circulating intracellular globin (Alvinella pompejana and Glycera dibranchiata), noncirculating intracellular globin (Arenicola marina myoglobin) and extracellular globin from various annelids share a similar gene structure, with two conserved introns at canonical positions B12.2 and G7.

Gene structure and molecular phylogeny of the linker chains from the giant annelid hexagonal bilayer hemoglobins.

Giant extracellular hexagonal bilayer hemoglobin (HBL-Hb), found only in annelids, is an approximately 3500-kDa heteropolymeric structure involved in oxygen transport. The HBL-Hbs are comprised of globin and linker chains, the latter being required for the assembly of the quaternary structure. The linker chains, varying in size from 225 to 283 amino acids, have a conserved cysteine-rich domain within their N-terminal moiety that is homologous to the cysteine-rich modules constituting the ligand binding domain of the low-density lipoprotein receptor (LDLR) protein family found in many metazoans.

The multigenic family of the extracellular hemoglobin from the annelid polychaete Arenicola marina.

The extracellular hemoglobin of the lugworm Arenicola marina which inhabits on the intertidal area, a sulfide-rich environment, comprises eight globin chains previously determined by mass spectrometry. We have cloned and sequenced five of the globin components. The deduced amino-acid sequences exhibit an extracellular signal peptide and two cysteine residues involved in an internal disulfide bond.