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Local infiltration of neuropeptide Y as a potential therapeutic agent against apoptosis and fibrosis in a swine model of hypercholesterolemia and chronic myocardial ischemia.

Abstract：

:While the angiogenic effects of Neuropeptide Y (NPY) in myocardial ischemia and hypercholesterolemia have been studied, its effects on altering oxidative stress, fibrosis and cell death are not known. We hypothesized that local infiltration of NPY in a swine model of chronic myocardial ischemia and hypercholesterolemia will induce nerve growth and cell survival, while reducing oxidative stress and fibrosis. Yorkshire mini-swine (n=15) were fed a high cholesterol diet for 5 weeks. Three weeks after surgical induction of focal myocardial ischemia, an osmotic pump was implanted, which delivered NPY (n=8, high cholesterol treated, HCT) or the vehicle (n=7, high cholesterol control, HCC) for 5 weeks. Then myocardium was harvested for analysis. Assessment of myocardial function and perfusion was made the last intervention. Immunoblotting demonstrated significantly decreased levels of MMP-9 (p=0.001) and TGF-β (p=0.05) and significantly increased levels of Ang-1 (p=0.002), MnSOD (p=0.006) and NGF (p=0.01) in HCT. Immunohistochemistry results revealed significantly decreased TUNEL staining (p=0.005) and GLUT4 translocation (p=0.004) in HCT. The functional data showed significantly improved blood flow reserve (p=0.02) and improved diastolic function -dP/dt (p=0.009) in the treated animals. Local infiltration of NPY results in positive remodeling in ischemic myocardium in the setting of hypercholesterolemia. By initiating angio and neurogenesis, NPY infiltration improves blood flow reserve and restoration of fatty acid metabolism. The associated increased cell survival and decreased fibrosis result in improved myocardial diastolic function. NPY may have a potential therapeutic role in patients with hypercholesterolemia associated coronary artery disease.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Matyal R,Sakamuri S,Wang A,Mahmood E,Robich MP,Khabbaz K,Hess PE,Sellke FW,Mahmood F

doi

10.1016/j.ejphar.2013.08.023

subject

Has Abstract

pub_date

2013-10-15 00:00:00

pages

261-70

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(13)00613-4

journal_volume

718

pub_type

杂志文章

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Local infiltration of neuropeptide Y as a potential therapeutic agent against apoptosis and fibrosis in a swine model of hypercholesterolemia and chronic myocardial ischemia.