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A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
A new chromogranin A-dependent angiogenic switch activated by thrombin
Luca Crippa1, Mimma Bianco, Barbara Colombo
1Tumor Biology and Vascular Targeting Unit, Division of Molecular Oncology, San Raffaele Scientific Institute, Milan, Italy.
Blood
|November 30, 2012
Summary
Chromogranin A (CgA) inhibits blood vessel formation. Thrombin cleavage activates pro-angiogenic fragments, suggesting a balance regulated by proteolysis that may trigger angiogenesis in certain diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Vascular Biology
Background:
- Angiogenesis is tightly regulated by pro- and anti-angiogenic factors.
- Chromogranin A (CgA), a neuroendocrine protein, is found in circulation.
- The role of CgA in angiogenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of circulating chromogranin A (CgA) in angiogenesis.
- To identify the functional domains of CgA responsible for its anti-angiogenic activity.
- To explore the impact of CgA cleavage on its angiogenic properties.
Main Methods:
- In vitro and in vivo angiogenesis models.
- Structure-activity relationship studies of CgA.
- Hematologic analysis of circulating CgA forms.
- Thrombin-mediated cleavage assays.
Main Results:
- Physiologic levels of CgA inhibit angiogenesis.
- The C-terminal region of CgA contains a functional anti-angiogenic site.
- Cleavage of CgA by thrombin generates pro-angiogenic fragments.
- Circulating CgA exists as a balance of anti- and pro-angiogenic forms, altered by coagulation.
Conclusions:
- CgA and its fragments form a balance of angiogenic factors regulated by proteolysis.
- Thrombin-induced alteration of this balance may promote angiogenesis in pathological conditions.
- CgA represents a novel target for modulating angiogenesis.
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