© Springer International Publishing AG 2017 83
T. Angelone et al. (eds.), Chromogranins: from Cell Biology to Physiology
and Biomedicine, UNIPA Springer Series, DOI 10.1007/978-3-319-58338-9_6
Chromogranin A in Endothelial Homeostasis
and Angiogenesis
Flavio Curnis, Fabrizio Marcucci, Elisabetta Ferrero, and Angelo Corti
Abstract The unbalanced production of factors capable of regulating vascular
homeostasis and angiogenesis is a common denominator of many pathological con-
ditions, including cardiovascular diseases, macular degeneration, rheumatoid arthri-
tis, neoplastic diseases and many others. Among the various regulatory factors so far
identified, chromogranin A (CgA), a protein released in circulation by many normal
and neoplastic cells of the diffuse neuroendocrine system, is emerging as an impor-
tant player. Indeed, a growing body of evidence suggests that circulating CgA and
its fragments contribute to the homeostatic regulation of the endothelial barrier
function and angiogenesis in normal conditions, and that alteration of their relative
levels, either by changes in their secretion or by extracellular proteolytic processing,
might represent important mechanisms that contribute to regulate angiogenesis.
Here, we review these studies and discuss the potential role of CgA and its frag-
ments as regulators of vascular physiology in cancer.
1 Introduction
It is well known that endothelial cells, either in physiological or pathological condi-
tions, can sense a number of factors released by other cells, locally or in circulation,
to regulate blood flow and tissue perfusion, its barrier function and transport of
plasma components to tissues, leucocyte adhesion and extravasation, angiogenesis
and tissue remodelling. For example, the formation of new blood vessels from pre-
existing vessels is tightly regulated by the coordinated action of anti- and pro-
angiogenic factors that are released by the endothelium or other cells (Ribatti 2009 ).
The unbalanced production of these factors is a common denominator of many
pathological conditions, including cardiovascular diseases, macular degeneration,
skin diseases, diabetic ulcers, stroke, rheumatoid arthritis, neoplastic diseases and
F. Curnis • E. Ferrero () • A. Corti ()
Division of Experimental Oncology, San Raffaele Scientific Institute,
via Olgettina, 58 Milan, Italy
e-mail: [email protected]; [email protected]
F. Marcucci
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy