Affiliation:
1. Department of Thoracic Cardiovascular Surgery Affiliated Hospital of Xuzhou Medical University Xuzhou China
2. Morphological Research Experiment Center Xuzhou Medical University Xuzhou China
Abstract
Background
We previously found that the structural defects of the coronary collateral microcirculation reserve (
CCMR
) prevent these preformed collateral vessels from continuously delivering the native collateral blood and supporting the ischemic myocardium in rats. Here, we tested whether these native collaterals can be remodeled by artificially increasing pigment epithelium–derived factor (
PEDF
) expression and demonstrated the mechanism for this stimulation.
Methods and Results
We performed intramyocardial gene delivery (
PEDF
‐lentivirus, 2×10
7
TU) along the left anterior descending coronary artery to artificially increase the expression of
PEDF
in the tissue of the region for 2 weeks. By blocking the left anterior descending coronary artery, we examined the effects of
PEDF
on native collateral blood flow and
CCMR
. The results of positron emission tomography perfusion imaging showed that
PEDF
increased the native collateral blood flow and significantly inhibited its decline during acute myocardial infarction. In addition, the number of
CCMR
vessels decreased and the size increased. Similar results were obtained from in vitro experiments. We tested whether
PEDF
induces
CCMR
remodeling in a fluid shear stress–like manner by detecting proteins and signaling pathways that are closely related to fluid shear stress. The nitric oxide pathway and the Notch‐1 pathway participated in the process of
CCMR
remodeling induced by
PEDF
.
Conclusions
PEDF
treatment activates the nitric oxide pathway, and the Notch‐1 pathway enabled
CCMR
remodeling. Increasing the native collateral blood flow can promote the ventricular remodeling process and improve prognosis after acute myocardial infarction.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
13 articles.
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