# Effect of Physical Exercise on the Release of Micorparticles with Angiogenic Potential
## 2 Vasculogenesis, Arteriogenesis, and Angiogenesis  
Vessels can be formed mainly by three processes: vasculogenesis, arteriogenesis, and angiogenesis. Vasculogenesis is the formation of new vessels that occurs in the embryo as well in the fetal annexes involved in the transportation of maternal nutrients: the placental villi and the yolk sac [18]; it derives from the differentiation of mesodermal cells into angioplasty, that proliferate, migrate, and couple to produce a primitive tube-like vessel. Consequently, vessels continue to develop as angioplasty differentiate in endothelial cells, form a vascular lumen, and deposit the basal lamina [19]. Various growth factors are involved in the molecular signaling of vasculogenesis: the fibroblast growth factor (FGF)-2, involved in mesodermal induction as well as in the induction of the angioplasty from the mesoderm [20], VEGFs family, that plays a pivotal role for its stimulating effects, [21], and finally the transforming growth factor-\(\beta\) family (TGF-\(\beta\)s) that contributes to vasculogenesis, with a dose dependent effect (low doses stimulate, while high doses inhibit endothelial cell growth [22]).  
Arteriogenesis is the process whereby small pre-existing arterioles are transformed in functional arteries. One of the major stimuli inducing arteriogenesis is represented by shear stress, a mechanical signal able to activate transcription factors such as early growth response protein-1 (erg-1), that in turn lead to gene expression of chemokines like monocyte chemoattractant protein-1 (MCP-1), and adhesion molecules like intercellular adhesion molecule-1 (ICAM-1). These molecules are important for the docking of monocytes on endothelial cells, a fundamental step in arteriogenesis. Moreover, also growth factors such as VEGF, FGF, and TGF-\(\beta\) are involved in this process [23; 24].  
Lastly, angiogenesis is the process in which new blood vessels rising from pre-existing vessels, and it can occur mainly through mechanisms such as sprouting and intussusception (also known as vessel splitting or non-sprouting angiogenesis) [25]. Angiogenesis is a fundamental process during embryonic, fetal, and adult life and plays a pivotal role in many physiological process (e.g., as in skeletal growth, in wound healing, in pregnancy); however, angiogenesis represents also an important hallmark of pathological processes such as cancer and several noncommunicable diseases. Angiogenesis is governed by a precise balance between angiogenic growth factors and inhibitors. VEGF-A and its tyrosine kinase receptors represent the main and best characterized signaling pathway involved in developmental angiogenesis [26]. However, other molecules play a key role in endothelial cell proliferation and migration. They are represented by FGFs, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) [27]. Therefore, angiogenesis is a complex process controlled by several molecules and can have useful as well as detrimental effects on human health, and for this reason the various underlying mechanisms are object of great interest.