Abstract

Background: Stem cell therapy of acute myocardial infarction (AMI) is proving to be a promising approach to repair the injured myocardia. The time window for stem cell transplantation is crucial yet difficult to determine since it produces different therapeutic effects at different times after myocardial infarction. Stromal cell-derived factor-1 (SDF- 1) plays a pivotal role in the mobilization, homing, proliferation, and differentiation of transplanted stem cells. Here, by using ultrasound molecular imaging via targeted microbubbles, we determined the dynamic expression of SDF-1 in a swine model of AMI in vivo. Methods: Twenty-four miniswine were randomly selected for the control group and the AMI model group, which underwent ligation of the left anterior descending coronary artery (LAD). The AMI animals were randomly divided into six experimental groups according to the duration of the myocardial infarction. All animals were subjected to ultrasound molecular imaging through injections with targeted microbubbles (T + T group) or nontargeted control microbubbles (T + C group). The values of the myocardial perfusion parameters (A, β, and A × β) were determined using Q-Lab (Philips ultrasound, version 9.0), and the expression level of SDF-1 was analyzed by real-time polymerase chain reaction (RT-PCR). Results: Our results showed that the expression of SDF-1 gradually increased and peaked at 1 week after AMI. The trend is well reflected by ultrasound molecular imaging in the myocardial perfusion parameters. The A, β, and A × β values correlated with SDF-1 in the T + T group (r = 0.887, 0.892, and 0.942; P < 0.05). Regression equations were established for the relationships of the A, β, and A × β values (X) with SDF-1 (Y): Y = 0.699X − 0.6048, Y = 0.4698X + 0.3282, and Y = 0.0945X + 0.6685, respectively (R 2 = 0.772, 0.7957, and 0.8871; P < 0.05). Conclusions: Our finding demonstrated that ultrasound molecular imaging could be used to evaluate the expression dynamics of SDF-1 after AMI.

Highlights

  • Acute myocardial infarction (AMI), which is defined as myocardial cell death caused by prolonged ischemia, is one of the leading causes of cardiovascular disease mortality worldwide (Mozaffarian et al, 2016)

  • Our results showed that the expression of Stromal cell-derived factor-1 (SDF-1) gradually increased and peaked at 1 week after AMI

  • Our finding demonstrated that ultrasound molecular imaging could be used to evaluate the expression dynamics of SDF-1 after AMI

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Summary

Introduction

Acute myocardial infarction (AMI), which is defined as myocardial cell death caused by prolonged ischemia, is one of the leading causes of cardiovascular disease mortality worldwide (Mozaffarian et al, 2016). There is evidence to demonstrate that both stem cell types can differentiate toward cardiomyocytes and endothelial cells and can be home to damaged tissues in vivo (Oswald et al, 2004; Pittenger and Martin, 2004; Boyle et al, 2010; Naaijkens et al, 2012). These adult mesenchymal stem cells may secrete growth factors and cytokines that can stimulate cardiovascular repair through a paracrine effect. By using ultrasound molecular imaging via targeted microbubbles, we determined the dynamic expression of SDF-1 in a swine model of AMI in vivo

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