Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice

The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers predicting the risk of developing GI later in life...

Differential gene expression analysis of tubule forming and non-tubule forming endothelial cells: CDC42GAP as a counter-regulator in tubule formation

The formation of new tubular structures from a quiescent endothelial lining is one of the hallmarks of sprouting angiogenesis. This process can be mimicked in vitro by inducing capillary-like tubular structures in a three-dimensional (3D) fibrin matrix. We aimed to analyze the differential mRNA expression in two phenotypically distinct cell...

Vascular Growth in Ischemic Limbs: A Review of Mechanisms and Possible Therapeutic Stimulation

Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant further research. Here, current insights into...

TAFI and pancreatic carboxypeptidase B modulate in vitro capillary tube formation by human microvascular endothelial cells

OBJECTIVE - Besides having a key role in fibrinolysis, the plasminogen system has been implicated in cell migration and angiogenesis. A common mechanism is the binding of plasminogen to carboxy-terminal lysine residues in partially degraded fibrin or on cellular surfaces. Here we examined the involvement of thrombin activatable fibrinolysis...

Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFβ2 and FGF2

Objective: Examine effects of insulin-like growth factor 1 (IGF1), transforming growth factor β2 (TGFβ2) and fibroblast growth factor 2 (FGF2) on proteoglycan and collagen network and biomechanical properties of the newly formed cartilage matrix. Methods: Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without...

Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice

Fibroblast growth factor (FGF) receptor 3 has been identified as a key regulator of endochondral bone development and of post-natal bone metabolism through its action on growth plate chondrocytes and osteoblasts, respectively. It has also been shown to promote chondrogenesis and cartilage production by cultured pre-chondrogenic cells in response...

Ingrowth of aorta wall into stent grafts impregnated with basic fibroblast growth factor: A porcine in vivo study of blood vessel prosthesis healing

Objective: Endovascular aneurysm repair is an alternative treatment of abdominal aortic aneurysm. The procedure is less invasive, and morbidity and most probably mortality are reduced. However, some problems, such as endoleakage, are yet to be resolved. Endoleakage can occur after graft migration, as a result of insufficient fixation of the...

Aminopeptidase inhibitor bestatin stimulates microvascular endothelial cell invasion in a fibrin matrix

The aminopeptidase inhibitor bestatin has been shown to have anti-angiogenic effects in a number of model systems. These effects are thought to result from inhibition of CD13 activity. Because tumor angiogenesis can evolve in a fibrin-rich stroma matrix we have studied for the first time the effects of bestatin on microvascular endothelial...

Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix

Adult angiogenesis, associated with pathologic conditions, is often accompanied by the formation of a fibrinous exudate. This temporary matrix consists mainly of fibrin but is intermingled with plasma proteins and collagen fibers. The formation of capillary structures in a fibrinous matrix in vivo was mimicked by an in vitro model, in which...

Ingrowth of aorta vascular cells into basic fibroblast growth factor-impregnated vascular prosthesis material: A porcine and human in vitro study on blood vessel prosthesis healing

Objective: One of the most life-threatening vascular diseases is rupture of an abdominal aneurysm. The conventional treatment is based on surgical reconstruction. An alternative treatment is endovascular aneurysm repair (EVAR). Despite many advantages, one of the problems of EVAR is endoleakage from deficient healing between the aortic neck and...

Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions and intratumoral fluid

Purpose: On the basis of the finding of marked overexpression in angiogenic microvessels, aminopeptidase N/CD13 has recently been suggested to play a prominent role in tumor angiogenesis. A soluble form of CD13 (sCD13) is present in human plasma, but its role in cancer has not been addressed. We hypothesized that sCD13 would be shed by tumor...

Impact of apolipoprotein(a) on in vitro angiogenesis

Angiostatin, which consists of the kringle I-IV domains of plasminogen and which is secreted into urine, is an efficient inhibitor of angiogenesis and tumor growth. Because N-terminal apolipoprotein(a) [apo(a)] fragments, which also contain several types of kringle IV domains, are found in urine as well, we evaluated the potential angiostatic...

Proteolysis of the urokinase-type plasminogen activator receptor by metalloproteinase-12: Implication for angiogenesis in fibrin matrices

Pericellular proteolysis plays an important role in cell migration and the formation of new capillary structures. The plasminogen activator/plasmin and matrix degrading metalloproteinase (MMP) cascades act together in the remodeling of matrix and cell-matrix contacts. Previously we have shown that the formation of capillary structures by human...

Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: Implications for capillary-like tube formation in a fibrin matrix

Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth factor-2 (FGF-2) or vascular endothelial growth...

Effect of steroid hormones and retinoids on the formation of capillary-like tubular structures of human microvascular endothelial cells in fibrin matrices is related to urokinase expression

Angiogenesis, the formation of new capillary blood vessels, is a feature of a variety of pathological processes. To study the effects of a specific group of hormones (all ligands of the steroid/retinoid/thyroid hormone receptor superfamily) on the angiogenic process in humans, we have used a model system in which human microvascular endothelial...

Genistein reduces tumor necrosis factor α-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells

The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PAI-1 induced by these inflammatory...