Article

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

Beth Israel Deaconess Medical Center, Department of Anesthesia and Critical Care
European journal of pharmacology (Impact Factor: 2.68). 09/2013; 718(1-3). DOI: 10.1016/j.ejphar.2013.08.023
Source: PubMed

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 five 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 five 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 results in improved myocardial diastolic function. NPY may have a potential therapeutic role in patients with hypercholesterolemia associated coronary artery disease.

0 Followers
 · 
76 Views
  • Source
    • "NPY initiated angiogenesis leads to improved vascular reserve and less oxidative stress on the mitochondria thus shifting cellular metabolism back to fatty acid oxidation and increasing markers of cell survival. The NPY related remodeling led to neurogenesis and angiogenesis possibly causing increased cell survival and decreased fibrosis thus improving diastolic function [42]. Majority of above mentioned measurements have been done in acute phase of ischemia. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides - Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy-diabetic, ischemic, inflammatory, stress-induced or restricitive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.
    Peptides 08/2014; 61. DOI:10.1016/j.peptides.2014.08.004 · 2.61 Impact Factor
  • Source
    • "NPY initiated angiogenesis leads to improved vascular reserve and less oxidative stress on the mitochondria thus shifting cellular metabolism back to fatty acid oxidation and increasing markers of cell survival. The NPY related remodeling led to neurogenesis and angiogenesis possibly causing increased cell survival and decreased fibrosis thus improving diastolic function [42]. Majority of above mentioned measurements have been done in acute phase of ischemia. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides - Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy-diabetic, ischemic, inflammatory, stress-induced or restricitive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.
    Peptides 08/2014; · 2.61 Impact Factor