Role of Peptide YY in blood vessel function and atherosclerosis in a rabbit model

Abstract

Cardiovascular disease remains a burden for Westernized countries. Peptide YY (PYY) raises blood pressure, yet its role has not yet been determined in diseased arteries. This study aimed at identifying PYY and eNOS in diseased blood vessels and to determine which blood vessels respond to PYY. New Zealand White rabbits were fed an atherogenic diet (n = 6, 0.5% cholesterol + 1% methionine + 5% peanut oil) and control animals fed a normal diet (n = 6) for 4 weeks. Immunohistochemistry was used to determine the localization of PYY and eNOS in the aorta. The aorta, carotid, renal, iliac, inferior mesenteric, and renal interlobular arteries were removed, mounted in organ baths, and subjected to doses of PYY (10(-9) -10(-7) mol/L) and then acetylcholine (10(-6) mol/L). Immunohistochemistry of the aorta shows PYY staining in plaque macrophages, smooth muscle cells and endothelium, and these cells co-expressed eNOS. PYY caused a minor vasoconstrictive response in all blood vessels studied but was blunted in arteries from control animals. Acetylcholine caused relaxation of PYY constricted blood vessels. This data clearly shows that PYY is present in atherosclerotic plaque and is a minor constrictor of the vasculature tree. Further studies aimed at understanding the role of PYY in cardiovascular disease are warranted.

Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction

“…Consistent with others, we found PYY serum levels to increase with age and to be elevated in patients with diabetes, which has similarly been reported by some [20] although not all investigators [21]. In addition, arterial hypertension was more often present in patients with high PYY levels, which might be attributable to direct vasoconstrictive effects of the peptide resulting in increased blood pressure under experimental conditions [22,23]. Furthermore, more patients with impaired kidney function had elevated PYY levels in our study, which is consistent with earlier findings of elevated PYY levels in patients with terminal renal insufficiency [24].…”

PYY is a negative regulator of bone mass and strength

“…Nevertheless, at P186 when cortical mineralisation was increased in Pyy KO mice, toughness did not differ from WT animals indicating that bone strength and toughness is determined by a complex interplay between cortical diameter, thickness, mineralisation and porosity. Previous studies have shown PYY mediates vasoconstriction via Y1 or Y2 receptor [42] consistent with the increased cortical vessel size in P186 Pyy KO mice . Furthermore, the increase in cortical vessel number in P70 Pyy KO mice suggests PYY may also inhibit angiogenesis during bone growth.…”

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

“…On the other hand, species from Proteobacteria produce serotonin, NE, and DA [170], which are neurotransmitters with pro-hypertensive and pro-atherogenic properties [171][172][173], with the exception of DA [174][175][176]. Furthermore, the gut microbiota controls the endocrine activities of the intestine; for example, SCFAproducing bacteria, which are reduced in CVD cases [28,151,153,154], promote secretion of incretins with cardioprotective, antiatherogenic, and antihypertensive properties [177][178][179][180], except for PYY [181,182]. Therefore, the gut dysbiosis seen in CVD cases gives rise to an endocrine environment favoring CVD development.…”