Key result
Cardiac-selective expression of human secretory leukocyte protease inhibitor via AAV9 vector significantly reduced myocardial infarct size (32.69% vs 50.68%, p<0.05) and improved cardiac function in a rat model of ischemia/reperfusion injury.
Why the study?
Previous studies demonstrated the cardioprotective effect of SLPI against I/R injury, but SLPI gene overexpression in cardiovascular diseases had only been investigated in vitro.
Does AAV9-mediated cardiac-selective expression of hSLPI reduce myocardial ischemia/reperfusion injury in a rat model?
Does AAV9-mediated cardiac-selective expression of hSLPI reduce myocardial ischemia/reperfusion injury in a rat model?
Cardiac-selective gene delivery of hSLPI via AAV9 provides cardioprotection against myocardial ischemia/reperfusion injury in an in vivo rat model by reducing infarct size, inflammation, and oxidative stress.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for cardiac SLPI overexpression in I/R injury; prospective trials needed before clinical consideration.
Protease enzymes contribute to the initiation of cardiac remodeling and heart failure after myocardial ischemic/reperfusion (I/R) injury. Protease inhibitors attenuate protease activity and limit left ventricular dysfunction and remodeling. Previous studies showed the cardioprotective effect of secretory leukocyte protease inhibitor (SLPI) against I/R injury. However, overexpression of SLPI gene in cardiovascular diseases has only been investigated in an in vitro experiment. Here, cardiac-selective expression of the human secretory leukocyte protease inhibitor (hSLPI) gene and its effect on I/R injury were investigated. Adeno-associated virus (AAV) serotype 9 carrying hSLPI under the control of cardiac-selective expression promoter (cardiac troponin, cTn) was intravenously administered to Sprague–Dawley rats for 4 weeks prior to coronary artery ligation. The results showed that myocardial-selective expression of hSLPI significantly reduced infarct size, cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and myoglobin levels that all served to improve cardiac function. Moreover, overexpression of hSLPI showed a reduction in inflammatory cytokines, oxidatively modified protein carbonyl (PC) content, ischemia-modified albumin (IMA), and necrosis and cardiac tissue degeneration. In conclusion, this is the first study to demonstrate cardiac-selective gene delivery of hSLPI providing cardioprotection against myocardial I/R injury in an in vivo model.
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Mongkolpathumrat et al. (2022) studied Myocardial ischemia/reperfusion injury (n=39). AAV9-cTnT-hSLPI vs. AAV9 control viral particles was evaluated on Infarct size (% of area at risk) (p=<0.05). Cardiac-selective expression of human secretory leukocyte protease inhibitor via AAV9 vector significantly reduced myocardial infarct size (32.69% vs 50.68%, p<0.05) and improved cardiac function in a rat model of ischemia/reperfusion injury.
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