Enhanced angiogenesis and increased cardiac perfusion after myocardial infarction in protein tyrosine phosphatase 1B‐deficient mice

• DOI: 10.1096/fj.13-245753
• Publication Date: 2014-04-24T09:37:31Z
• Authors: Marie Besnier; Ariane Galaup; Lionel Nicol; Jean‐Paul Henry; David Coquerel; Alexandre Gueret; Paul Mulder; Ebba Brakenhielm; Christian Thuillez; Stéphane Germain; Vincent Richard; Antoine Ouvrard‐P...
• Keywords: [SDV.BIO]Life Sciences [q-bio]/Biotechnology; Cardiotonic Agents; [SDV.IMM] Life Sciences [q-bio]/Immunology; [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]; Myocytes, Smooth Muscle; Myocardial Infarction; Neovascularization, Physiologic; Mice; 03 medical and health sciences; [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system; Cell Movement; Diastole; Coronary Circulation; growth factors; [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]; Animals; Molecular Targeted Therapy; Aorta; Cells, Cultured; Heart Failure; Mice, Knockout; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Mice, Inbred BALB C; 0303 health sciences; Endothelial Cells; [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences; cytokines; 3. Good health; [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system; [SDV.BIO] Life Sciences [q-bio]/Biotechnology; Capillaries; [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences; Arterioles; [SDV.IMM]Life Sciences [q-bio]/Immunology; vascular growth; Cell Division

The protein tyrosine phosphatase 1B (PTP1B) modulates kinase receptors, among which is the vascular endothelial growth factor receptor type 2 (VEGFR2), a key component of angiogenesis. Because PTP1B deficiency in mice improves left ventricular (LV) function mo after myocardial infarction (MI), we hypothesized that enhanced angiogenesis early MI via activated VEGFR2 contributes to this improvement. At 3 d MI, capillary density was increased at infarct border PTP1B–/– [+ 7±2% vs. wild-type (WT), P = 0.05]. This associated with extracellular signal-regulated phosphorylation and activation (i.e., phosphorylated-Src/Src/VEGFR2 dissociation VEGFR2/VE-cadherin), together higher infiltration proangiogenic M2 macrophages within unchanged overall infiltration. In vitro, showed inhibition or silencing using RNA interference VEGF-induced migration proliferation mouse heart microvascular cells as well fibroblast (FGF)-induced rat aortic smooth muscle cells. 8 mice, LV (+21 ±3% WT; P<0.05) an number small diameter arteries (15-50 μm) were likely participate perfusion assessed by magnetic resonance imaging improved compliance, indicating reduced diastolic dysfunction. conclusion, reduces MI-induced failure promptly ischemia enhancing angiogenesis, perfusion, function.—Besnier, M., Galaup, A., Nicol, L., Henry, J.-P, Coquerel, D., Gueret, Mulder, P., Brakenhielm, E., Thuillez, C., Germain, S., Richard, V., Ouvrard-Pascaud, A. Enhanced cardiac 1B-deficient mice. FASEB J. 28, 3351–3361 (2014). www.fasebj.org