A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 38/27 (2006.01) A61K 38/25 (2006.01) A61P 9/10 (2006.01) C07K 14/61 (2006.01)
Patent
CA 2399548
Growth hormone releasing peptides (GHRPs), a family of synthetic analogs modelled from Met-enkephalin, have been found to bind a novel class of specific GHRP receptors in the mammalian heart that are distinct from the pituitary GHRP receptors involved in GH secretion. CD36, a multifunctional B-type scavenger receptor, has been identified as the unique GHRP binding site in the heart. CD36 mediates the uptake of lipoproteins into a number of cell types and was recognized to play a crucial role in scavenging oxidized low density lipoproteins in monocyte/ macrophages leading to foam cell formation, a key step in fatty streaks formation. The hexapeptide GHRP prototypes hexarelin (His - DMe - Trp - Ala - Trp - D Phe - Lys - NH2) and EP 80317 (Haic-D Me - Trp -D Lys - Trp - D Phe- Lys - NH2), the latter analog being devoid of GH-secreting activity in vivo, have been shown to reduce fatty streak lesions and hypercholesterolemia in apolipoprotein E (Apo E) null mice fed a high fat high cholesterol diet (HFHC). In addition, non-HDL cholesterol was significantly decreased, whereas HDL cholesterol tended to increase. GHRP treatment also inhibited oxLDL-induced monocyte chemotaxis in the peritoneal cavity, which was associated with a reduced expression of the CD36 protein on peritoneal monocytes/macrophages. GHRPs may represent a novel therapeutic avenue to reduce the severe morbidity associated with the arterial disease atherosclerosis and its complications, such as myocardial infarction and strokes, that occur despite current management strategies.
Marleau Sylvie
Ong Huy
Tremblay Andre
Goudreau Gage Dubuc
Marleau Sylvie
Ong Huy
Tremblay Andre
Universite de Montreal
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