PDGFBB Increases Myocardial Production of VEGF: Shift in VEGF mRNA Splice Variants after Direct Injection of bFGF, PDGFBB, and PDGFAB

Affleck, David G.; Bull, David A.; Bailey, Stephen; Albanil, Aida; Connors, Rafe C.; Stringham, James C.; Karwande, Shreekanth V.

doi:10.1006/jsre.2002.6510

Cited by 20 publications

(13 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with previous results, 8 24 hours after MI, injection of NF/PDGF significantly improved left ventricular Table 1). Improvement of fractional shortening was sustained over 3 months in MIϩNF/PDGF animals compared with controls (Table 1).…”

Section: Local Delivery Of Pdgf Improves Long-term Cardiac Performancesupporting

confidence: 91%

Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity

et al. 2006

View full text Add to dashboard Cite

Background— Local delivery methods can target therapies to specific tissues and potentially avoid toxicity to other organs. Platelet-derived growth factor can protect the myocardium, but it also plays an important role in promoting pulmonary hypertension. It is not known whether local myocardial delivery of platelet-derived growth factor during myocardial infarction (MI) can lead to sustained cardiac benefit without causing pulmonary hypertension. Methods and Results— We performed a randomized and blinded experiment of 127 rats that survived experimental MI or sham surgery. We delivered platelet-derived growth factor (PDGF)-BB with self-assembling peptide nanofibers (NFs) to provide controlled release within the myocardium. There were 6 groups with n≥20 in each group: sham, sham+NF, sham+NF/PDGF, MI, MI+NF, and MI+NF/PDGF. Serial echocardiography from 1 day to 3 months showed significant improvement of ventricular fractional shortening, end-systolic dimension, and end-diastolic dimension with local PDGF delivery ( P <0.05 for MI+NF/PDGF versus MI or MI+NF). Catheterization at 4 months revealed improved ventricular function in the controlled delivery group (left ventricular end-diastolic pressure, cardiac index, +dP/dt, −dP/dt, and time constant of exponential decay all P <0.05 for MI+NF/P versus MI or MI+NF). Infarcted myocardial volume was reduced by NF/PDGF therapy (34.0±13.3% in MI, 28.9±12.9% in MI+NF, and 12.0±5.8% in MI+NF/PDGF; P <0.001). There was no evidence of pulmonary toxicity from the therapy, with no differences in right ventricular end-systolic pressure, right ventricular dP/dt, bromodeoxyuridine staining, or pulmonary artery medial wall thickness. Conclusions— Intramyocardial delivery of PDGF by self-assembling peptide NFs leads to long-term improvement in cardiac performance after experimental infarction without apparent pulmonary toxicity. Local myocardial protection may allow prevention of heart failure without systemic toxicity.

show abstract

Section: Local Delivery Of Pdgf Improves Long-term Cardiac Performancesupporting

confidence: 91%

Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Our in vitro and in vivo data are in accord. The vasculogenic/angiogenic effect of PDGF-BB in heart explants revealed in this study may be attributable to the ability of PDGF-BB to induce marked increases in VEGF as demonstrated in rabbit hearts 18 and retinal pigment cells. 26 An earlier in vitro study showed that the PDGFR-␤ receptor is specific for endothelial tube formation and is responsive to PDGF-BB.…”

Section: Vasculogenesis/angiogenesismentioning

confidence: 61%

“…15,16 A role for PDGF-BB and PDGFR-␤ in myocardial vasculogenesis/angiogenesis has been suggested because all cell types that contribute to the coronary vasculature express this ligand and receptor in the embryonic avian heart, 17 and PDGF-BB enhances the production of VEGF in the myocardium. 18 FGF-2 is a regulator of both angiogenesis and arteriogenesis (reviewed in Presta et al), 19 as it has been shown to enhance endothelial and smooth muscle cell proliferation. 20,21 We have documented a role for FGF-2 in embryonic myocardial tubulogenesis 5 and postnatal arteriogenesis.…”

mentioning

confidence: 99%

Temporally Expressed PDGF and FGF-2 Regulate Embryonic Coronary Artery Formation and Growth

Tomanek¹,

Hansen²,

Christensen³

2008

ATVB

View full text Add to dashboard Cite

Objective-PDGF and FGF-2 are important regulators of vascular wall assembly. We tested the hypothesis that their embryonic temporal expression facilitates 2 specific events: (1) the endothelial invasion of the aortic root to form the coronary artery stems and (2) the subsequent growth and development of the arterial tree. Methods and Results-Addition of FGF-2 and PDGF-BB proteins to embryonic quail heart explants stimulated a 3-and 7-fold increase, respectively, in tubulogenesis, whereas neutralizing antibodies to these growth factors attenuated tubulogenesis by 40%. Anti-FGF-2 and anti-PDGF neutralizing antibodies were then introduced in ovo via the vitelline vein at various embryonic (E) days. When injections occurred before coronary ostial formation, the embryos usually developed only 1 coronary artery or lacked coronary arteries. When 1 or both major coronary arteries formed: (1) their branches had a thinner tunica media, and (2) smooth muscle investment did not progress as far distally as in shams. Other anomalies included smaller diameter coronary artery stems in some hearts. Inhibition of VEGF via injections of aflibercept (VEGF-Trap, a VEGFR-1 and -2 chimera), previously shown to be essential for coronary stem formation, limited development of the coronary arteries even though introduced after formation of coronary ostia (at E9 or EI0). Conclusions-Our data (1) document a role for FGF-2 and PDGF in the temporal regulation of coronary artery stem formation and growth of the coronary arterial tree and (2) reveal that VEGF expression is required for normal artery/arterial formation, even after coronary artery stem formation.

show abstract

“…Yet, it has several distinct variants, such as VEGFA121, VEGFA145, VEGFA148, VEGFA165, VEGFA183, VEGFA189 and VEGFA206, which occur as a consequence of alternative splicing (1). Many reports demonstrated that each isoform is differentially regulated, depending on its physiological situation (5–7). …”

Section: Introductionmentioning

confidence: 99%

Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis

Wang

Tsai

2016

Nucleic Acids Research

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Previous studies focused on transcriptional regulation modulated by proximal upstream cis-regulatory elements (CREs) of the human vegfa promoter. However, we hypothesized that distal upstream CREs may also be involved in controlling vegfa transcription. In this study, we found that the catalytic domain of Seryl-tRNA synthetase (SerRS) interacted with transcription factor Yin Yang 1 (YY1) to form a SerRS/YY1 complex that negatively controls vegfa promoter activity through binding distal CREs at −4654 to −4623 of vegfa. Particularly, we demonstrated that the −4654 to −4623 segment, which predominantly controls vegfa promoter activity, is involved in competitive binding between SerRS/YY1 complex and NFKB1. We further showed that VEGFA protein and blood vessel development were reduced by overexpression of either SerRS or YY1, but enhanced by the knockdown of either SerRS or yy1. In contrast, these same parameters were enhanced by overexpression of NFKB1, but reduced by knockdown of nfkb1. Therefore, we suggested that SerRS does not bind DNA directly but form a SerRS/YY1 complex, which functions as a negative effector to regulate vegfa transcription through binding at the distal CREs; while NFKB1 serves as a positive effector through competing with SerRS/YY1 binding at the overlapping CREs.

show abstract

PDGFBB Increases Myocardial Production of VEGF: Shift in VEGF mRNA Splice Variants after Direct Injection of bFGF, PDGFBB, and PDGFAB

Cited by 20 publications

References 30 publications

Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity

Local Controlled Intramyocardial Delivery of Platelet-Derived Growth Factor Improves Postinfarction Ventricular Function Without Pulmonary Toxicity

Temporally Expressed PDGF and FGF-2 Regulate Embryonic Coronary Artery Formation and Growth

Competitive binding between Seryl-tRNA synthetase/YY1 complex and NFKB1 at the distal segment results in differential regulation of human vegfa promoter activity during angiogenesis

Contact Info

Product

Resources

About