Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation

Weis, Michael; Pehlivanli, Sinan; Meiser, Bruno; Scheidt, Wolfgang von

doi:10.1016/s0735-1097(01)01430-9

Cited by 121 publications

(72 citation statements)

References 15 publications

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“…29 Moreover, simvastatin treatment has been associated with improvement in coronary artery function together with decreased cytokine activation in patients after heart transplantation. 30 Our results extend these conclusions and demonstrate that the benefits of statin treatment may also occur in the immediate postoperative period after CABG. In the present study, statin treatment was associated with lowered adhesion of activated neutrophils to vascular endothelium after hypoxia/reoxygenation, by a mechanism involving reduced expression of both neutrophil CD11b and endothelial P-selectin.…”

Section: Discussionsupporting

confidence: 83%

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass

Chello

Mastroroberto²,

Patti³

et al. 2003

Heart

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Objective: To investigate the effects of preoperative simvastatin treatment on leucocyte-endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass. Design: Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions. Setting: University hospital (tertiary referral centre). Patients: Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls. Main outcome measures: Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium. Results: Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin. Conclusions: Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.

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Section: Discussionsupporting

confidence: 83%

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass

Chello

Mastroroberto²,

Patti³

et al. 2003

Heart

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“…These results are consistent with the observation in other studies that statin treatment reduced plasma levels of C-reactive protein, a marker of inflammation (96,97). Protective effects of simvastatin on coronary vasomotor function and the transcardiac gradient (i.e., coronary release) of IL-6 and TNF␣ were also noted in cardiac transplant recipients without angiographically detectable disease, suggesting that endothelial functions are improved and inflammatory cytokine release is reduced (98). However, because improved endothelial function and reduced inflammation may also be due to lipid-lowering effects of statins, the reduction of mortality and arterial pathology in heart transplant recipients cannot be attributed to cholesterolindependent effects of statins alone, much less to specific immunosuppressant effects.…”

Section: Evidence For Immunomodulatory Effects Of Statins In Humanssupporting

confidence: 92%

Immunomodulatory Effects of Statins

Palinski

Tsimikas²

2002

Journal of the American Society of Nephrology

109

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Abstract. Clinical trials with statins have demonstrated a marked reduction of cardiovascular mortality. However, it remains controversial whether these clinical benefits stem from powerful cholesterol-lowering effects of statins or whether they are due in part to their cholesterol-independent effects on vascular function, plaque growth, plaque rupture, or thrombosis. The identification of several mechanisms through which statins decrease the recruitment of monocytes and T cells into the arterial wall and inhibit T cell activation and proliferation in vitro have prompted speculations that immunomodulatory effects of statins may be beneficial in recipients of organ transplants. Hypercholesterolemia is frequent in these patients, and delayed-type hypersensitivity reactions in the arterial walls of the graft may be compounded by chronic inflammation associated with conventional atherogenesis. To assess the potential clinical relevance of immunomodulatory effects of statins, the role of the immune system in atherogenesis and the effects of statins in vitro in experimental models and in clinical trials will be reviewed. It is concluded that despite solid in vitro evidence, clinical evidence for an independent immunosuppressive effect of statins in organ transplant patients is presently insufficient; however, further investigation of their in vivo occurrence and clinical relevance is warranted.

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“…44 Coronary allograft endothelial dysfunction is associated with circulating endothelin levels, 45 enhanced graft cytokine activation, 46 and CMV infection, 47 whereas statin treatment reduces the progression of epicardial and microvascular dysfunction. 48 Coronary endothelial dysfunction predicts the development of intimal thickening 49 and predicts cardiovascular end points after HTx. 50 These data implicate endothelial dysfunction in the development of clinically significant CAV.…”

Section: Detection Of Coronary Vasomotor Alterationsmentioning

confidence: 99%

Cardiac Allograft Vasculopathy

2008

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Abstract-Cardiac allograft vasculopathy (CAV) continues to limit the long-term success of cardiac transplantation.Recent insights have underscored the fact that innate and adaptive immune responses are involved in the pathogenesis of CAV. Vascular lesions are the result of cumulative endothelial injuries induced both by alloimmune responses and by nonspecific insults (including ischemia-reperfusion injury, viral infections, and metabolic disorders) in the context of impaired repair mechanisms. Intravascular ultrasound is the most sensitive method for detection of CAV, and progressive intimal thickening in the first posttransplant year identifies patients at high risk for future cardiovascular events. Encouraging results with regard to the detection of CAV by noninvasive methods should be an incentive to apply routine noninvasive imaging during mid-to long-term follow-up. Improved immunosuppressive drugs, including mycophenolate mofetil and proliferation signal inhibitors, as well as statins (in part via immunomodulation), have beneficial effects on CAV progression, although there is still a need to confirm the impact of vasodilators in improving outcome after heart transplantation. Coronary revascularization for CAV is only palliative, with no long-term survival benefit. Three main strategies for CAV prevention are currently under investigation: inhibition of growth factors and cytokines, cell therapy, and tolerance induction. However, because individual responses to an allograft change over time, assays to monitor the recipient's immune response and individualized methods for therapeutic immune modulation are clearly needed. (Circulation. 2008;117:2131-2141.)

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Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation

Cited by 121 publications

References 15 publications

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass

Immunomodulatory Effects of Statins

Cardiac Allograft Vasculopathy

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