PubMed Health⌕ Search

PubMed · 15544033

Myocardial angiogenesis.

Abstract

Coronary angiogenesis and collateral growth are chronic adaptations to myocardial ischemia, which are aimed at restoring coronary blood flow and salvaging myocardium in an ischemic region. Although we have assumed that myriad numbers of growth factors are involving in this adaptation, details in the underlying mechanisms, i.e., number of angiogenic factors, angiostatic factors, their receptors/signaling cascades, interactions/crosstalk among the signaling pathways and receptors, and the time course of expression/function of a particular factor or pathway during the successful adaptation are still unclear; they are, probably, harmonized like a symphony. Although there is as of yet no consensus about the mechanisms and causal factors for these cononary adaptations to ischemia, recent evidence strongly suggests that a balance between growth factors and growth inhibitors is critical. In this review we introduce vascular endothelial growth factor, angiopoietins, and angiostatin, as factors playing pivotal roles in coronary angiogenesis and collateral growth.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Eiji Toyota, Toshiro Matsunaga, William M Chilian. 2004. Myocardial angiogenesis.. https://doi.org/10.1023/b%3Amcbi.0000044372.65864.18

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Angiopoietin chemotactic activities on neutrophils are regulated by PI-3K activation.

Angiopoietins (Ang1 and Ang2) modulate blood vessel integrity during the angiogenic process through the activation of tyrosine kinase receptor (Tie2). We recently detected Tie2 expression on neutrophils and reported that angiopoietins induce acute proinflammatory events including neutrophil beta2-integrin activation and their adhesion onto endothelial cells. Herein, we investigated the effect of angiopoietins on neutrophil migration and their capacity to modulate CXCL8/IL-8 chemotactic properties. Using a Boyden chamber assay, we observed that Ang1 and Ang2 (up to 10 nM; 60 min) increased the migration of neutrophils, and the maximal effect was achieved at 1 nM (72% and 114% increase, respectively) as compared with untreated cells. Angiopoietins induce a rapid and transient Akt phosphorylation, and pretreatment of neutrophils with PI-3K inhibitors, wortmannin (100 nM) and LY294002 (500 nM), reduced Ang1-mediated neutrophil migration by 100% and 78% and Ang2 chemotactic activity by 100% and 71%, respectively. Treatment of neutrophils with CXCL8/IL-8 (up to 50 nM; 60 min) increased basal neutrophil migration by 257% at its optimal concentration (10 nM), and pretreatment of neutrophils with corresponding PI-3K inhibitors reduced CXCL8/IL-8 (1 nM) chemotactic effect. Pretreatment of neutrophils with Ang1 or Ang2 (10 nM; 15 min) potentiated neutrophil migration induced by CXCL8/IL-8 (1 or 10 nM; 60 min) by 263% and 238% and by 177% and 164%, respectively. Finally, both angiopoietins showed a synergistic effect on the induction of Akt phosphorylation mediated by CXCL8/IL-8. In summary, our data demonstrate that angiopoietins increase neutrophil migration through PI-3K activation and can enhance proinflammatory activities of other cytokines.

Angiopoietins↗

In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic vessels in mouse airways and skin.

OBJECTIVE: We investigated and compared the in vivo effects of all four angiopoietins (COMP-Ang1, Ang2, Ang3, and Ang4) on blood and lymphatic vascular remodeling in adult mice. We analyzed the microvasculature of trachea and ear skin, and compared quiescent skin microvasculature with that during wound healing. METHODS AND RESULTS: We were able to achieve similar levels of relatively long-term and sustained circulating expression of each angiopoietin using an adenoviral delivery system. Two weeks after treatment, we observed tracheal blood and lymphatic vascular enlargement, and lymphatic filopodia formation, with the following order of potency: COMP-Ang1>Ang3=Ang4>Ang2. Co-treatment with Ang2 attenuated Ang1-induced tracheal blood and lymphatic remodeling. In the normal ear skin, all angiopoietins induced blood vessel enlargement, whereas none induced lymphatic vascular remodeling. However, in the healing margin of ear skin wounds, all angiopoietins strongly induced lymphatic vascular enlargement and formation of lymphatic sprouts and filopodia, while they potentiated blood vascular enlargement. Co-treatment of Ang2 with Ang1 produced an additive effect on these changes. CONCLUSION: This study, one of the first to our knowledge to characterize the in vivo actions of all 4 angiopoietins, may expand the current concepts for use of angiopoietins for therapeutic angiogenesis and lymphangiogenesis.

Angiopoietins↗

Angiogenesis - understanding the mathematical challenge.

Biological mathematics is based on the development of mathematical descriptions of biological systems and behaviour. We are interested in developing mathematical models of capillary sprouting, and have adopted a novel approach to our modelling, in that the mathematics is based on the biochemistry underpinning cell behaviour. By considering the crucial steps of the angiogenic process, and through an understanding of the biochemistry involved, we successfully developed a preliminary model of angiogenesis. More importantly, our approach is applicable to many other areas of biological research. As mathematics remains a mystery to the majority of life scientists, we have aimed to describe our mathematical modelling strategy in biological terms. The assumptions and simplifications that form the basis of the modelling are explained, pinpointing the manner in which the different biological processes are linked via the mathematics. Examples of simulations using the mathematical model are shown, highlighting the success of our approach.

Angiopoietins↗