Angiopoietins(ANGPT) and their endothelial cell-specific tyrosine kinase receptors TEK are the major regulators of blood vessels angiogenesis under physiological and pathologic conditions. ANGPT1 is essentially involved in maturation, stabilization, and remodeling of blood vessels through inducing TEK autophosphorylation, promoting endothelial cell migration and survival. Instead, ANGPT2 appears to act as a natural antagonist of ANGPT1, it can activate vascular remodeling with the presence of vascular endothelial growth factor(VEGF) or regress frank blood vessels under the absence of VEGF. High expression of angiopoietins and TEK is often detected in tumor tissues. Many studies showed that disrupting the ANGPT/TEK receptor pathway could inhibit the growth of a number of murine tumors and human tumors. Thus, it is possible that inhibitors targeting the ANGPT/TEK pathway will have broad clinical utility to treatment of cancer.
Angiopoietin-1 ; physiology ; Angiopoietin-2 ; physiology ; Angiopoietins ; physiology ; Humans ; Neovascularization, Physiologic ; physiology ; Receptor, TIE-2 ; physiology

Angiopoietin-1 ; chemistry ; physiology ; Angiopoietin-2 ; chemistry ; physiology ; Angiopoietins ; physiology ; Animals ; Cardiovascular Diseases ; therapy ; Embryonic and Fetal Development ; Humans ; Neoplasms ; blood supply ; Receptor, TIE-2 ; chemistry ; physiology ; Signal Transduction

OBJECTIVETo study the effect of dexamethasone on airway morphology and on the expression of angiopoietin-1 (Ang-1) and its tyrosine kinase receptor Tie-2 in the airway of asthmatic rats.

METHODSForty-five Sprague-Dawley rats were randomly divided into control, asthmatic, and dexamethasone-treated asthmatic groups. Asthma was induced by repeated sensitization and challenge with ovalbumin in the latter two groups. The dexamethasone intervention group received an intraperitonea injection of dexamethasone (2 mg/kg) before asthma challenge. Immunohistochemistry was used to measure the expression of Ang-1 and Tie-2 in the airway. Airway thickness was estimated by a computerized digital image analyzer.

RESULTSAirway thickness in the asthmatic group (33.9333+/-8.3791 micro m2/micro m) increased significantly compared with that in the control group (21.1333+/-2.7740 micro m2/micro m) (P<0.01). The dexamethasone intervention group also showed increased thickness of the airway (27.4000 +/- 4.6105 micro m2/micro m) compared with the control group (P<0.01), but the airway thickness in the dexamethasone intervention group was significantly reduced compared with that in the untreated asthmatic group (P<0.01). The expression of Ang-1 (103.9487+/-8.2914 vs 76.0320+/-3.7728; P<0.01) and Tie-2 (99.2307+/-8.1913 vs 75.3153+/-3.7321; P<0.01) in the airway increased significantly in the asthmatic group compared to controls. The expression of Ang-1 and Tie-2 in the airway of the dexamethasone intervention group (90.6180+/-5.2339 and 86.6633+/-3.7321, respectively) was statistically higher than that in the control group (P<0.01) but statistically lower than that in the untreated asthmatic group (P<0.01). Ang-1 and Tie-2 expression in the airway was positively correlated with the thickness of airway (r(Ang)-1=0.719r(Tie)-2=0.746P<0.01). There was also a positive correlation between Ang-1 and Tie-2 expression (r=0.742P<0.01).

CONCLUSIONSThe expression of Ang-1 and Tie-2 in the airway increased in asthmatic rats and was positively correlated with the thickness of the airway. Ang-1 and Tie-2 may participate in the process of airway remodeling in asthma. Dexamethasone can decrease the expression of Ang-1 and Tie-2 in the airway and relieve the changes of airway morphology.

Angiopoietin-1 ; analysis ; physiology ; Animals ; Asthma ; metabolism ; pathology ; Female ; Lung ; chemistry ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptor, TIE-2 ; analysis ; physiology

Angiopoietin-1 (Ang1) binds to and activates Tie2 receptor tyrosine kinase. Ang1-Tie2 signal has been proposed to exhibit two opposite roles in the controlling blood vessels. One is vascular stabilization and the other is vascular angiogenesis. There has been no answer to the question as to how Tie2 induces two opposite responses to the same ligand. Our group and Dr. Alitalo's group have demonstrated that trans-associated Tie2 at cell-cell contacts and extracellular matrix (ECM)-anchored Tie2 play distinct roles in the endothelial cells. The complex formation depends on the presence or absence of cell-cell adhesion. Here, we review how Ang1-Tie2 signal regulates vascular maintenance and angiogenesis. We further point to the unanswered questions that must be clarified to extend our knowledge of vascular biology and to progress basic knowledge to the treatment of the diseases in which Ang1-Tie2-mediated signal is central.
Angiopoietin-1/*physiology ; Animals ; Cell Adhesion/physiology ; Cell Movement/physiology ; Endothelial Cells/*physiology ; Endothelium, Vascular/physiology ; Extracellular Matrix/*metabolism ; Humans ; Neovascularization, Physiologic/physiology ; Receptor, TIE-2/*physiology ; Signal Transduction/*physiology

Angiopoietins ; metabolism ; physiology ; Animals ; Cell Proliferation ; Endothelial Cells ; cytology ; physiology ; Humans ; Neoplasms ; blood supply ; Neovascularization, Pathologic ; physiopathology ; Neovascularization, Physiologic ; physiology ; Pericytes ; cytology ; metabolism ; physiology ; Proto-Oncogene Proteins c-sis ; metabolism ; physiology ; Receptor, Platelet-Derived Growth Factor beta ; metabolism ; physiology ; Receptor, TIE-2 ; metabolism ; physiology ; Signal Transduction