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Enhanced angiogenesis and increased cardiac perfusion after myocardial infarction in protein tyrosine phosphatase 1B-deficient mice.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2014 Aug; Vol. 28 (8), pp. 3351-61. Date of Electronic Publication: 2014 Apr 23. - Publication Year :
- 2014
-
Abstract
- The protein tyrosine phosphatase 1B (PTP1B) modulates tyrosine 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 2 mo after myocardial infarction (MI), we hypothesized that enhanced angiogenesis early after MI via activated VEGFR2 contributes to this improvement. At 3 d after MI, capillary density was increased at the infarct border of PTP1B(-/-) mice [+7±2% vs. wild-type (WT), P = 0.05]. This was associated with increased extracellular signal-regulated kinase 2 phosphorylation and VEGFR2 activation (i.e., phosphorylated-Src/Src/VEGFR2 and dissociation of endothelial VEGFR2/VE-cadherin), together with higher infiltration of proangiogenic M2 macrophages within unchanged overall infiltration. In vitro, we showed that PTP1B inhibition or silencing using RNA interference increased VEGF-induced migration and proliferation of mouse heart microvascular endothelial cells as well as fibroblast growth factor (FGF)-induced proliferation of rat aortic smooth muscle cells. At 8 d after MI in PTP1B(-/-) mice, increased LV capillary density (+21±3% vs. WT; P<0.05) and an increased number of small diameter arteries (15-50 μm) were likely to participate in increased LV perfusion assessed by magnetic resonance imaging and improved LV compliance, indicating reduced diastolic dysfunction. In conclusion, PTP1B deficiency reduces MI-induced heart failure promptly after ischemia by enhancing angiogenesis, myocardial perfusion, and diastolic function.<br /> (© FASEB.)
- Subjects :
- Animals
Aorta
Arterioles physiopathology
Capillaries physiopathology
Cardiotonic Agents pharmacology
Cell Division
Cell Movement
Cells, Cultured
Diastole
Endothelial Cells pathology
Heart Failure etiology
Heart Failure physiopathology
Heart Failure prevention & control
Mice
Mice, Inbred BALB C
Mice, Knockout
Molecular Targeted Therapy
Myocardial Infarction complications
Myocardial Infarction enzymology
Myocytes, Smooth Muscle cytology
Protein Tyrosine Phosphatase, Non-Receptor Type 1 deficiency
Protein Tyrosine Phosphatase, Non-Receptor Type 1 genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 1 physiology
RNA Interference
Rats
Signal Transduction
Vascular Endothelial Growth Factor Receptor-2 physiology
Ventricular Dysfunction, Left etiology
Ventricular Dysfunction, Left physiopathology
Ventricular Remodeling
Coronary Circulation physiology
Myocardial Infarction physiopathology
Neovascularization, Physiologic physiology
Protein Tyrosine Phosphatase, Non-Receptor Type 1 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 28
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 24760754
- Full Text :
- https://doi.org/10.1096/fj.13-245753