Roles of Vascular Endothelial Growth Factor in Amyotrophic Lateral Sclerosis

Table 1

Different members of ligands of VEGF family and characteristics and properties.

Ligand	Chromosomal localization	Protein; molecular weight	Isoforms	Expression sites High levels of expression	Role/remarks	Receptors	References
VEGF-A	6p21.3; (8 exons, 7 introns)	Dimeric glycoprotein; 33–42 kDa; Precursor protein-232 aa	Human; VEGF121 (VEGF121b^∗); VEGF145 (VEGF145b^∗); VEGF148, VEGF165 (VEGF165b^∗) VEGF183 (VEGF183b^∗); VEGF189 (VEGF189b^∗); VEGF206; Mice: VEGF120, VEGF164, VEGF188; (alternative mRNA splicing)	Adrenal gland, lung; kidney, heart	Angiogenesis, survival, neuronal development,; increased migration, and proliferation of endothelial cells; Vasodilation (by inducing the endothelial nitric oxide synthase and increasing nitric oxide production); Monocyte motility	VEGFR-1; sVEGFR-1; VEGFR-2; NRP-1; NRP-2 (VEGF145, VEGF165)	[46, 49, 50, 58, 63, 70]
Placental growth factor (PlGF)	14q24; (7 exons)	Homodimeric glycoprotein; 45 kDa; 131 aa (PlGF-1); 152 aa (PlGF-2)	PLGF-1 (PLGF 131); PLGF-2 (PLGF 152); PLGF-3 (PLGF 203); PLGF-4 (PLGF 224); (alternative mRNA splicing)	Placenta, lungs, heart, skeletal muscle, thyroid gland, adipose tissue, retina, skin, ECs, trophoblasts monocytes, erythroid cells	Regulation of vascular differentiation, vasculogenesis,; angiogenesis during inflammation, wound healing, ischemia, and cancer	VEGFR-1; NRP-1 (PLGF-2)	[49, 56, 57, 59–65, 70]
VEGF-B	11q13; (7 exons, 6 introns)	21 kDa; 167 aa; (VEGF-B167); 32 kDa; 186 aa (VEGF-B186); 188 aa	VEGF-B167 and VEGF-B186; (alternative mRNA splicing)	Myocardium, skeletal muscle, pancreas,; neural tissues (retina, brain, and spinal cord), smooth muscle cells of large vessels, prostate, brown fat	Embryonic angiogenesis,; mitogenic factor for human ECs,; strong cell survival factor for different types of cells: neurons, vascular cells (pericytes, EC, and smooth muscle cells), and myocytes	VEGFR-1; sVEGFR-1; NRP-1	[50, 56, 57, 63, 66–74, 216]
VEGF-C	4q34; (7 exons)	29–31 kDa; 20 kDa mature protein; 399 aa	VEGF-C62, VEGF-C129, and VEGF-C184 (from immortalized mouse)-splicing isoforms; Proteolytic mechanisms	High levels: heart, ovary, placenta, skeletal muscle, thyroid gland, and small intestine; Modest transcripts: kidney, lung, pancreas, prostate, spleen	Angiogenesis and lymphangiogenesis; (mitogenesis, the mature form of VEGF-C induces migration and survival of ECs and induces selective lymphangiogenesis without accompanying angiogenesis)	VEGFR-2; VEGFR-3	[50, 56, 57, 63, 70, 72, 76, 77, 79–81, 276]
VEGF-D	Xp22.31; (7 exons)	Glycoprotein; human cDNA encodes protein; 354 aa	Two isoforms,; Proteolytic mechanisms	High levels: Heart, lungs, skeletal muscle, colon, and small intestine; Modest transcripts: ovary, pancreas, prostate, spleen, testes	Angiogenesis and lymphangiogenesis; (induces proliferation, survival, and migration of lymphatic ECs)	VEGFR-2; VEGFR-3	[50, 56, 57, 63, 70, 72, 75–82, 85]
VEGF-E	Non-human; Orf parapoxvirus	120–140 aa	VEGF-ENZ-2; VEGF-ENZ-7; VEGF-ENZ-10; VEGF-ED1701; VEGF-EVR634	ds DNA parapoxvirus	Potent angiogenic activity growth, vascular permeability, proliferation, migration, sprouting, and mitotic activity of vascular ECs, stimulates chemotaxis	VEGFR-2; NRP-1	[49, 56, 57, 63, 81, 86, 92]
VEGF-F/Trimeresurus flavoviridis svVEGF (T.f. svVEGF)	Non-human	110–122 aa Functions as dimmers-2 proteins: Vammin (110 residues aa); VR-1 (109 residues aa)		Isolated from snake venom: svVEGF from Bothrops insularis TfsvVEGF (Trimeresurus flavoviridis svVEGF); from pit vipers	Weak angiogenic activity; Strong vascular permeability activity; Induces hypotension	VEGFR-1	[49, 56, 63, 81, 87]

aa: amino acids.
Ec: endothelial cell.
VEGF_𝑋𝑋𝑋: the number of amino acids on the polypeptide chain.
* VEGF_{𝑋𝑋𝑋b}: Antiangiogenic isoforms.