Plasminogen Activator Inhibitor-1 Regulates Myoendothelial Junction Formation

Heberlein, Katherine R.; Straub, Adam C.; Best, Angela K.; Greyson, Mark A.; Looft‐Wilson, Robin; Sharma, Poonam; Meher, Akshaya K.; Leitinger, Norbert; Isakson, Brant E.

doi:10.1161/circresaha.109.215723

Cited by 46 publications

(90 citation statements)

References 47 publications

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“…A recent report has also indicated the importance of PAI-1 in myoendothelial junction formation. 19 Further studies in animals with atherosclerosis or myocardial infarction are needed to demonstrate the potential beneficial effects of arteriogenesis on myocardial function.…”

Section: Discussionmentioning

confidence: 99%

“…We also saw the induction of plasminogen activator inhibitor (PAI)-1, which is involved in matrix remodeling and, for example, myoendothelial junction formation. 19 Immunostaining revealed that PAI-1 was expressed mainly in the arterial walls ( Figure 4C). Resorcin Fuchsin staining for elastin indicated that most of the smooth muscle cell proliferation had occurred in the media of the arteries of 1-month-old VEGF-B TG hearts, whereas some fragmentation of the internal elastic lamina was seen in many of the arteries from 4-month-old TG rats ( Figure 3E, white arrowheads).…”

Section: The Vegf-b Transgene Induces Strong Coronary Arteriogenesis mentioning

confidence: 99%

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Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation

et al. 2010

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Background— Vascular endothelial growth factor-B (VEGF-B) binds to VEGF receptor-1 and neuropilin-1 and is abundantly expressed in the heart, skeletal muscle, and brown fat. The biological function of VEGF-B is incompletely understood. Methods and Results— Unlike placenta growth factor, which binds to the same receptors, adeno-associated viral delivery of VEGF-B to mouse skeletal or heart muscle induced very little angiogenesis, vascular permeability, or inflammation. As previously reported for the VEGF-B 167 isoform, transgenic mice and rats expressing both isoforms of VEGF-B in the myocardium developed cardiac hypertrophy yet maintained systolic function. Deletion of the VEGF receptor-1 tyrosine kinase domain or the arterial endothelial Bmx tyrosine kinase inhibited hypertrophy, whereas loss of VEGF-B interaction with neuropilin-1 had no effect. Surprisingly, in rats, the heart-specific VEGF-B transgene induced impressive growth of the epicardial coronary vessels and their branches, with large arteries also seen deep inside the subendocardial myocardium. However, VEGF-B, unlike other VEGF family members, did not induce significant capillary angiogenesis, increased permeability, or inflammatory cell recruitment. Conclusions— VEGF-B appears to be a coronary growth factor in rats but not in mice. The signals for the VEGF-B–induced cardiac hypertrophy are mediated at least in part via the endothelium. Because cardiomyocyte damage in myocardial ischemia begins in the subendocardial myocardium, the VEGF-B–induced increased arterial supply to this area could have therapeutic potential in ischemic heart disease.

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Section: Discussionmentioning

confidence: 99%

Section: The Vegf-b Transgene Induces Strong Coronary Arteriogenesis mentioning

confidence: 99%

Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation

et al. 2010

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“…Vascular Cell Co-culture Assay and cGMP MeasurementsTo test the effect of ZINC39395747 on NO diffusion, a vascular cell co-culture assay was constructed as previously described (10,25,26). In brief, rat renal ECs and rat preglomerular VSMCs were isolated as previously described (24,27,28) and co-cultured for 3 days to allow for the formation of myoendothelial junctions.…”

Section: Methemoglobin Formation Assay In Mouse Rbcsmentioning

confidence: 99%

Structure Guided Chemical Modifications of Propylthiouracil Reveal Novel Small Molecule Inhibitors of Cytochrome b5 Reductase 3 That Increase Nitric Oxide Bioavailability

Rahaman¹,

Reinders²,

Koes³

et al. 2015

Journal of Biological Chemistry

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“…Electron Microscopy: All tissues were processed and stained for immunogoldtransmission electron microscopy as previously described [211]. Quantification of gold beads in endothelium (EC), at the myoendothelial junction (MEJ), or vascular smooth muscle cells (VSMC) was performed as previously described [211] lfonicacid (HEPES) and 6 D-glucose, pH 7.4 with NaOH) containing sodium nitroprusside followed by fixation with 4% PFA.…”

Section: Experimental Methodologies In the Study Of CX And Panx Functmentioning

confidence: 99%

“…Quantification of gold beads in endothelium (EC), at the myoendothelial junction (MEJ), or vascular smooth muscle cells (VSMC) was performed as previously described [211] lfonicacid (HEPES) and 6 D-glucose, pH 7.4 with NaOH) containing sodium nitroprusside followed by fixation with 4% PFA. The arteries were removed, cut longitudinally and conventional immunocytochemistry was performed (as described above).…”

Section: Experimental Methodologies In the Study Of CX And Panx Functmentioning

confidence: 99%

Function and Regulation of Pannexin 1 Channels in the Vascular Endothelium

Lohman¹

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The nucleotide adenosine 5'-triphosphate (ATP) has classically been considered the cell's primary energy currency; however, a novel role for ATP as an extracellular autocrine/paracrine signaling molecule has evolved over the past century. Purinergic signaling is now known to regulate a plethora of physiological and pathophysiological processes in almost every organ system. In the vasculature, ATP and its metabolites elicit dual control over blood vessel tone and tissue perfusion, and purinergic signaling events have been implicated in vascular pathologies including atherosclerosis and inflammation.While the importance of extracellular ATP in the vascular system is well recognized, the mechanism(s) mediating the regulated release of the purine from vascular cells are less well understood and are a key target of current investigation. One such ATP-liberation mechanism has been ascribed to the recently identified pannexin (Panx) channels, namely Panx1. Initially, we characterized the expression and localization profiles of Panx isoforms across the systemic vasculature, identifying predominant representation by the Panx1 isoform in both smooth muscle (SMC) and endothelial cells (EC) comprising the blood vessel wall, with more heterogeneous expression profiles observed in specialized vascular systems including the heart, lung and kidney. In particular, the Panx1 isoform is highly expressed in ECs regardless of blood vessel type or size, while Panx1 expression is limited to SMCs of small arteries and arterioles. Panx1 forms hexameric channels in the plasma membrane of ECs, functioning to release ATP in response to a number of stimuli. However, prolonged Panx1 channel activity is extremely detrimental to cell viability. Here we report a novel negative regulatory mechanism that may govern the activity of Panx1 channels in ECs, by which the bioactive gas nitric oxide (NO) covalently modifies two cysteine (Cys) residues in the channel by a process termed S- reinforce the dual effect of purines on peripheral resistance and blood pressure. Purinergic Control of Vascular InflammationWhile the foundation for purinergic control of vascular functions was initially characterized extensively in the context of vascular reactivity and overall blood flow and pressure regulation, it has become increasingly clear that extracellular ATP also plays important regulatory roles in the vascular inflammatory response. Vascular inflammation can be characterized as acute (physiological) or chronic (pathological) in nature.The acute vascular inflammatory response is an innate process of inflammatory cell homing to infected or damaged tissues resulting from integrated cross-talk between circulating leukocytes and the vascular endothelium, primarily at the level of postcapillary venules [61]. This process has been highly studied and is now known to occur in a step-wise manner beginning with local recruitment, rolling (fast and slow), adhesion and final extravasation into the surrounding tissue (reviewed in [62...

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Plasminogen Activator Inhibitor-1 Regulates Myoendothelial Junction Formation

Cited by 46 publications

References 47 publications

Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation

Vascular Endothelial Growth Factor-B Acts as a Coronary Growth Factor in Transgenic Rats Without Inducing Angiogenesis, Vascular Leak, or Inflammation

Structure Guided Chemical Modifications of Propylthiouracil Reveal Novel Small Molecule Inhibitors of Cytochrome b5 Reductase 3 That Increase Nitric Oxide Bioavailability

Function and Regulation of Pannexin 1 Channels in the Vascular Endothelium

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