title: CD151 gene delivery after myocardial infarction promotes functional neovascularization and activates FAK signaling.
abstract: Our previous studies showed that tetraspanin CD151 promotes neovascularization in rat hindlimb and myocardial ischemia models. This study is to assess whether CD151 induces arteriogenesis and promotes functional neovascularization in a pig myocardial infarction model, and to determine the signaling pathways involved. CD151 cDNA and antiCD151 sequence were constructed into a recombinant adeno-associated virus (rAAV) vector. All 26 pigs used either were subjected to coronary artery ligation or did not undergo surgery. Eight wks after viral administration, the expression of CD151 protein was measured by Western blot. The densities of capillaries and arterioles were determined using immunohistochemistry. Regional myocardial perfusion and other myocardial functions were evaluated by (13)N-labeled NH(3) positron emission computed tomography ((13)N-NH(3) PET) and echocardiography. Western blot was performed for assessing the signaling mechanisms. Overexpression of CD151 markedly increased the densities of capillaries and arterioles, significantly enhanced the regional myocardial perfusion, reduced myocardial ischemia, and improved the myocardial contraction, wall motion, and wall thickness. Conversely, antiCD151 gene delivery reversed the above changes. In addition, CD151 activated focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), c-Jun N-teminal kinase (JNK), phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and endothelial nitric-oxide synthase (eNOS), and increased nitric oxide (NO) level. These findings demonstrate a robust role of CD151 in inducing and/or upregulating neovascularization. CD151-dependent neovascularization correlates with the activations of FAK, mitogen activated protein kinases (MAPKs), and PI3K signaling, suggesting that CD151 may promote neovascularization via MAPKs and PI3K pathways.
authors: Department of Cardiology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Houjuan
authors: H
authors: Zuo
authors: Zhengxiang
authors: Z
authors: Liu
authors: Xiaochun
authors: X
authors: Liu
authors: Jun
authors: J
authors: Yang
authors: Tao
authors: T
authors: Liu
authors: Sha
authors: S
authors: Wen
authors: Xin A
authors: XA
authors: Zhang
authors: Katherine
authors: K
authors: Cianflone
authors: Daowen
authors: D
authors: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006321:Heart / Q000502:physiology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D060185:Tetraspanin 24
chemical_list: D015703:Antigens, CD; C554717:Cd151 protein, rat; D011994:Recombinant Proteins; D060185:Tetraspanin 24; D019869:Phosphatidylinositol 3-Kinases; D051417:Focal Adhesion Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases