Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass

Pretorius, Mias; Donahue, Brian S.; Yu, Chang; Greelish, James P.; Roden, Dan M.; Brown, Nancy J.

doi:10.1161/circulationaha.106.677906

Cited by 52 publications

(54 citation statements)

References 37 publications

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“…TGF-␤1 released from platelets during trauma or surgery might also contribute to the transient increases in plasma levels of PAI-1 that occur after these phenomena if the released latent TGF-␤1 becomes activated intravascularly and systemically activates endothelial cells. [41][42][43][44][45][46][47] This would provide a valuable homeostatic link between platelet activation to arrest hemorrhage and transient inhibition of fibrinolysis to allow the early unopposed deposition of fibrin to secure hemostasis. In addition, the ability of shear force to activate latent TGF-␤1 makes TGF-␤1 a potential shear sensor in addition to being a cellular effector.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1

Ahamed

Burg

Yoshinaga

et al. 2008

Blood

136

163

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Transforming growth factor-␤1 (TGF-␤1) has potent physiologic and pathologic effects on a variety of cell types at subnanomolar concentrations. Platelets contain 40 times as much TGF-␤1 as other cells and secrete it as an inactive (latent) form in complex with latency-associated peptide (LAP), which is disulfide bonded via Cys33 to latent TGF-␤ binding protein 1 (LTBP-1). Little is known about how latent TGF-␤1 becomes activated in vivo.Here we show that TGF-␤1 released from platelets or fibroblasts undergoes dramatic activation when subjected to stirring or shear forces, providing a potential mechanism for physiologic control. Thioldisulfide exchange appears to contribute to the process based on the effects of thiol-reactive reagents and differences in thiol labeling of TGF-␤1 before and after stirring or shear. Activation required the presence of LTBP, as TGF-␤1 contained in complex with only LAP could not be activated by stirring when studied as either a recombinant purified protein complex or in the platelet releasates or sera of mice engineered to contain an LAP C33S mutation. Release IntroductionTransforming growth factor-␤1 (TGF-␤1) has potent physiologic and pathologic effects on a variety of cell types at subnanomolar concentrations, including cells of the immune and hematopoietic systems, as well as malignant cells and fibroblasts, 1 with the latter responding with increased collagen production leading to tissue fibrosis. 2 Nearly all cellular TGF-␤1 exists, however, in a biologically inactive (latent) form in a noncovalent complex with the remaining portion of its precursor molecule, latency-associated peptide (LAP), which is disulfide bonded to a latent TGF-␤ binding protein 3,or 4), forming the large latent complex (LLC). 3 Although much is known about the signaling mechanisms and downstream effects of TGF-␤1, 4 and several latent TGF-␤1 activating mechanisms have been identified in vitro (reviewed in Annes et al 3 ), little is known about the physiologic mechanisms that control latent TGF-␤1 activation in vivo. Recent data support activation of LLC TGF-␤1 via a traction mechanism, 3,[5][6][7][8][9][10][11] with LAP binding to integrins ␣V␤5, ␣V␤6, and ␣V␤8, and LTBP-1 binding to extracellular matrix.Blood platelets are a rich source of TGF-␤1, containing 40 to 100 times as much as other cells, 12 and releasing it when activated by a variety of agents, including thrombin, which is produced during blood clotting. [13][14][15][16][17][18][19] Virtually all of the TGF-␤1 released from platelets is in the LLC. 3,16 Because platelet latent TGF-␤1 is released into the circulation, and because traction on the molecule has been proposed as a mechanism of latent TGF-␤1 activation, 5,6 we hypothesized that intravascular shear force may serve as an analog of traction mediated by cellular contraction and contribute to the activation of latent TGF-␤1 released from platelets. We therefore tested this hypothesis by both in vitro and in vivo experiments. Methods Antibodies and reagentsAnti-TGF-␤1 (polyclonal chi...

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1

Ahamed

Burg

Yoshinaga

et al. 2008

Blood

136

163

View full text Add to dashboard Cite

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“…Alternately, another study showed that elevated serum interleukin-6 (IL-6) and CRP concentrations on postoperative day 1 were associated with the development of atrial fibrillation [18]. This is in distinction to a study, in which IL-6 was measured immediately after bypass and protamine administration, which failed to find similar associations between IL-6 and atrial fibrillation [19]. These different results may be due to the timing of the IL-6 determination, as IL-6 concentrations peak 4-6 h after surgery.…”

Section: Cardiac Surgerymentioning

confidence: 90%

Update on cardiac arrhythmias in the ICU

Goodman

Weiss

Weissman

2008

Current Opinion in Critical Care

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Supraventricular arrhythmias, especially atrial fibrillation, occur frequently in ICU patients. Intensivists not only treat atrial fibrillation itself but also its complications and the complications of the therapies used to prevent these complications. In ICU patients, ventricular arrhythmias have ominous implications because they usually portend either a major cardiac or a systemic dysfunction or both.

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“…[6][7][8][9] Obesity increases oxidative stress, endothelial dysfunction, and inflammation, 10,11 and systemic markers of these processes, including F 2 -isoprostanes, IL-6, and plasminogen activator inhibitor (PAI)-1, have been associated with BMI. 12,13 These markers also increase rapidly during cardiac surgery, [14][15][16] but their relation to AKI is not clear. If obesity is a risk factor for AKI, the identification of mechanisms by which obesity may affect AKI provides the opportunity to reduce AKI after cardiac surgery.…”

mentioning

confidence: 99%

Obesity and Oxidative Stress Predict AKI after Cardiac Surgery

Billings

Pretorius²,

Schildcrout³

et al. 2012

Journal of the American Society of Nephrology

Self Cite

143

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Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F 2 -isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m 2 [95% confidence interval, 4.3%-53.4%]; P=0.02).Baseline F 2 -isoprostane (P=0.04), intraoperative F 2 -isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F 2 -isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F 2 -isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.

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Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass

Cited by 52 publications

References 37 publications

In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1

In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1

Update on cardiac arrhythmias in the ICU

Obesity and Oxidative Stress Predict AKI after Cardiac Surgery

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