Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs.
Establishment of functional and stable collaterals in the ischemic myocardium is crucial to restoring cardiac function after myocardial infarction. Here, we show that only dual delivery of a combination of angiogenic and arteriogenic factors to the ischemic myocardium could significantly reestablish stable collateral networks and improve myocardial perfusion and function. A combination of FGF-2 with PDGF-BB, two factors primarily targeting endothelial cells and vascular smooth muscle cells, remarkably promotes myocardial collateral growth and stabilizes the newly formed collateral networks, which significantly restore myocardial perfusion and function. Using various members of the PDGF family together with FGF-2 in an angiogenesis assay, we demonstrate that PDGFR-alpha is mainly involved in angiogenic synergism, whereas PDGFR-beta mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease.
Lu
Huixia
H
Key Laboratory of Cardiovascular Remodelling and Function Research, Chinese Ministry of Education and Public Health, Qi Lu Hospital, Shandong University, Jinan 250012, Shandong Province, People's Republic of China.
Xu
Xinsheng
X
Zhang
Mei
M
Cao
Renhai
R
Bråkenhielm
Ebba
E
Li
Changjiang
C
Lin
Huili
H
Yao
Guihua
G
Sun
Huiwen
H
Qi
Lihang
L
Tang
Mengxiong
M
Dai
Hongyan
H
Zhang
Yanen
Y
Su
Runyi
R
Bi
Yanwen
Y
Zhang
Yun
Y
Cao
Yihai
Y
D043925:Angiogenesis Inducing Agents; D000792:Angiography; D000818:Animals; D000077214:Becaplermin; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D004452:Echocardiography; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D051379:Mice; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D013552:Swine
D043925:Angiogenesis Inducing Agents; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin