MedicalResearch.com Interview with:
Qing Kenneth Wang PhD, MBA
Huazhong University of Science and Technology
Wuhan, P. R. China and
Department of Molecular Cardiology
The Cleveland Clinic
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Coronary Artery Disease (CAD) and its complication myocardial infarction (MI or so called heart attacks) are the most common causes of deaths in the US and other parts of the world. Based on the American Heart Association statistics, 620,000 Americans have a new MI each year in the United States alone, 295 000 have a recurrent MI, and nearly 400,000 of them will die from it suddenly. Moreover, an estimated 150,000 silent first MI occur each year.
CAD and MI are caused by an occlusion or blockage of a coronary artery, which disrupts blood flow to the heart region, leading to damage or death of cardiac cells, impairment of cardiac function and sudden death. Current treatment of CAD and MI relies on reperfusion therapy with reopening of the occluded coronary artery with percutaneous coronary intervention (PCA) and coronary artery bypass surgery (CABG). However, 12% of patients are not candidates for PCA or CABG due to an unfavorable occlusive pattern, diffuse coronary atherosclerosis, small distant vessels and co-morbidities. An alternative revascularization strategy has to be developed to benefit these patients.
MedicalResearch.com: What should readers take away from your report?
Response: A collaborative team of scientists at Cleveland Clinic and Huazhong University of Science and Technology in China have discovered a new effective treatment for coronary artery disease (CAD) and heart attacks, as reported in the August 11, 2016 issue of PLOS Biology.
The new treatment for CAD and heart attacks is based on a gene named as AGGF1. The AGGF1 gene was discovered and cloned by Dr. Wang’s laboratory and reported in Nature in 2004. The AGGF1 gene codes for a protein that induces formation of new blood vessels, also referred to as an angiogenic factor. Dr. Wang’s group has continued to study the gene and its encoded protein for the last 12 years. They have knocked the gene out in mice (leading to deficiency of AGGF1) to study its physiological roles. When a heart attack is surgically created in AGGF1 knockout mice, the survival rate of Aggf1 KO mice is much worse than wild-type mice; the structure of the heart is damaged and the function of the heart is compromised.
Because AGGF knockout or deficiency was detrimental to the heart after MI, the scientists then reasoned that recombinant AGGF1 protein may be a valuable agent to treat MI. They created a mouse model for acute MI and tested the effectiveness of AGGF1 protein therapy. They found that AGGF1 protein therapy markedly reduced mortality and dramatically improved overall cardiac function and myocardial contraction by inhibiting cardiac hypertrophy, reducing infarct size, and preventing cardiac apoptosis and fibrosis in vivo.
In humans, there is a “scavenger” system called autophagy that is activated when tissue cells are injured and stressed by various physical or chemical factors. The “scavenger” system removes damaged cellular organelles or materials in cells and convert them into new energy and nutrition for reuse by cells. The “scavenger” system plays a protective role in the cell damage. The scientists find that the AGGF1 protein can trigger the activation of the “scavenger” system, then induce formation or generation of new blood vessels. The new blood vessels provide oxygen and nutrition to the heart and rescue the heart from damages from heart attacks. The AGGF1 treatment is particularly effective. The scientists think that the major reasons for the high success of the treatment are in two aspects: AGGF1 activates the “scavenger” system, which not only induces the formation of new blood vessels, but also protects cardiac cells from damages.
The AGGF1 protein therapy has a major advantage. Current treatment of CAD and MI like PCA and CABG does not eliminate blockage of small or microvessels, which can also be fatal in many cases. In theory, AGGF1 protein therapy can treat blockage of not only large vessels, but also small or microvessels.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Although the AGGF1 protein therapy is highly successful in animal models, it remains to be determined whether the technology can be translated to treat human patients with CAD and MI. The scientists are actively seeking industrial partners to move the technology to human trials.
MedicalResearch.com: Is there anything else you would like to add?
Response: Other major investigators of the study include Dr. Qiuyun Chen, an Assistant Professor at the Center for Cardiovascular Genetics, Department of Molecular Cardiology, Cleveland Clinic, Ph.D. students Qiulun Lu, Yufeng Yao, Zhengkun Hu, Changqing Hu, Qixude Song, and Jian Ye, and Associate Professor Chengqi Xu at Huazhong University of Science and Technology, and Annabel Z Wang at Duke University.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Qiulun Lu, Yufeng Yao, Zhenkun Hu, Changqing Hu, Qixue Song, Jian Ye, Chengqi Xu, Annabel Z. Wang, Qiuyun Chen, Qing Kenneth Wang. Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic Angiogenesis for Heart Disease. PLOS Biology, 2016; 14 (8): e1002529 DOI: 10.1371/journal.pbio.1002529
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