Circulating levels of the anti-angiogenic thrombospondin 2 are elevated in pre-eclampsia.
ABSTRACT An imbalance of maternal circulating pro- and anti-angiogenic factors may play a role in the pathogenesis of pre-eclampsia. Thrombospondin 2 (TSP-2) is a protein expressed mainly by activated endothelial cells, which acts as a potent anti-angiogenic agent. Our aim was to determine whether serum TSP-2 levels are altered in pre-eclampsia. We enrolled 35 pre-eclamptic patients and 35 healthy pregnant women in the study. Thrombospondin 2 levels were determined by enzyme-linked immunosorbent assay, while soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations were determined by electrochemiluminescence immunoassay. In patients with PE, we demonstrated 1.7-fold higher TSP-2 [13.2 (9.4-18.1) vs. 7.9 (7.2-11.2) ng/ml, p<0.001], 3.8-fold higher sFlt-1 and 4.3-fold lower PlGF levels compared with the control group. There were no associations between TSP-2 and sFlt-1 or PlGF concentrations. We suggest that circulating TSP-2 levels may contribute to the pathogenesis of PE via its anti-angiogenic properties, but in a distinct way from sFlt-1 and PlGF.
- [Show abstract] [Hide abstract]
ABSTRACT: Thrombospondin-1 and -2 (TSP-1 and -2) have been implicated in the regulation of angiogenesis, thrombosis, and inflammation, which are believed to be critical in the pathogenesis of cardiovascular events. The aim of this study was to assess whether serum TSP-1 and TSP-2 concentrations were associated with cardiovascular mortality in older men. A cohort of 992 elderly men was recruited between 2001 and 2004, and blood was collected for assessment of serum TSP-1 and TSP-2 by immunoassay. The men were followed by means of the Western Australia Data Linkage System until July 31, 2009. The association of TSP-1 and TSP-2 with mortality was assessed using Kaplan-Meier estimates and Cox proportional hazard analysis. Serum TSP-2 quartile was strongly positively associated with all-cause and cardiovascular mortality. Men with serum TSP-2 in the first, second, third, and fourth quartiles had a cumulative incidence of cardiovascular mortality of 3.3%, 8.0%, 9.7%, and 12.5% at 5 years, respectively, p = 0.001. Men with serum TSP-2 in the highest quartile had a 3.37-fold (95% confidence interval: 1.53-7.44, p = 0.003) increased risk of cardiovascular mortality after adjusting for other cardiovascular risk factors. Most deaths were secondary to cardiac causes, and serum TSP-2 was also independently associated with cardiac mortality (relative risk: 3.55, 95% confidence interval: 1.54-8.20 for men in the top compared with the lowest quartile). Serum TSP-1 was not associated with cardiovascular mortality. In conclusion, increased serum TSP-2 concentration is independently and significantly associated with the risk of cardiac mortality in older men.The American journal of cardiology 03/2013; · 3.58 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Abstract The aim of this study was to investigate the associations between insulin-like growth factor I (IGF-I) with vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sFlt-1) in umbilical serum and to study the effects of IGF-I upon sFlt-1 synthesis in human umbilical vein endothelial cells (HUVEC) in normotensive (NT) and preeclamptic (PE) pregnancies. As compared with the NT group, umbilical serum IGF-I and VEGF levels were lower in the PE group, while sFlt-1 concentrations were higher. Levels of sFlt-1 correlated with IGF-I in the NT group and with VEGF in the PE group. Basal concentration of sFlt-1 in HUVEC culture media was higher in the PE group. IGF-I stimulated sFlt-1 synthesis only in the NT group. In summary, umbilical serum sFlt-1 is associated with IGF-I in normotensive pregnancy and with VEGF in preeclampsia. IGF-I stimulates sFlt-1 synthesis in endothelial cells in normotensive but not in PE pregnancies.Growth factors (Chur, Switzerland) 06/2013; · 2.47 Impact Factor
Article: Revisiting the matricellular concept[Show abstract] [Hide abstract]
ABSTRACT: The concept of a matricellular protein was first proposed by Paul Bornstein in the mid-1990s to account for the non-lethal phenotypes of mice with inactivated genes encoding thrombospondin-1, tenascin-C, or SPARC. It was also recognized that these extracellular matrix proteins were primarily counter or de-adhesive. This review reappraises the matricellular concept after nearly two decades of continuous investigation. The expanded matricellular family as well as the diverse and often unexpected functions, cellular location, and interacting partners/receptors of matricellular proteins are considered. Development of therapeutic strategies that target matricellular proteins are discussed in the context of pathology and regenerative medicine.Matrix Biology. 01/2014;