Adenoviral VEGF-B186R127S gene transfer induces angiogenesis and improves perfusion in ischemic heart

iScience

Rahul Mallick¹  Kaisa Valli²  Mikko Hakulinen²  Jonna Airaksinen²  Olli-Pekka Hätinen²  Henna Korpela²  Tiina Nieminen²  Pyry Toivanen²  Seppo Ylä-Herttuala²  Pekka Poutiainen³  Jussi Nurro³ 

[1] Kuopio Center for Gene and Cell Therapy, Kuopio, Finland;A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland;Kuopio University Hospital, Kuopio, Finland;

关键词: Cellular therapy;    Biochemistry;    Molecular biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Vascular endothelial growth factor B (VEGF-B) is an interesting therapeutic candidate for coronary artery disease. However, it can also cause ventricular arrhythmias, potentially preventing its use in clinics. We cloned VEGF-B isoforms with different receptor binding profiles to clarify the roles of VEGFR-1 and Nrp-1 in angiogenesis and to see if angiogenic properties can be maintained while avoiding side effects. VEGF-B constructs were studied in vivo using adenovirus (Ad)-mediated intramyocardial gene transfers into the normoxic and ischemic porcine heart (n = 51). It was found that the unprocessed isoform VEGF-B186R127S is as efficient angiogenic growth factor as the native VEGF-B186 in normoxic and ischemic heart. In addition, AdVEGF-B186R127S increased myocardial perfusion reserve by 22% in ischemic heart without any side effects. AdVEGF-B127 (VEGFR-1 and Nrp-1 ligand) and AdVEGF-B109 (VEGFR-1 ligand) did not induce angiogenesis. Thus, VEGF-B186 is angiogenic only before its proteolytic processing to VEGF-B127. Only the VEGF-B186 C-terminal fragment was associated with arrhythmias.

【 授权许可】

Unknown