Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Tepperman, Elissa; Tumiati, Laura C.; Ramzy, Danny; Badiwala, Mitesh; Sheshgiri, Rohit; Prodger, Jessica L.; Ross, Heather J.; Rao, Vivek

doi:10.1016/j.healun.2010.11.022

Cited by 8 publications

(10 citation statements)

References 22 publications

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“…Patients with low cumulative exposure to tacrolimus showed similar levels of endothelial activation markers to those with higher cumulative exposure to tacrolimus. This is in agreement with some studies suggesting that tacrolimus may have beneficial effects on endothelial function [43]. Specifically, tacrolimus decreases the production of cytokines such as TNF‐alfa and IL‐6, and reduces the expression of adhesion molecules VCAM‐1, ICAM‐1, and E‐selectin in vitro [44].…”

Section: Discussionsupporting

confidence: 90%

HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation

et al. 2021

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Summary The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF‐alfa, IL‐6, IL‐8, and MCP‐1) and endothelial activation (E‐selectin, ICAM‐1, VCAM‐1, and MMP‐9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non‐transplanted HCV‐infected patients (LT‐/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV‐). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV‐ patients. However, levels of E‐selectin, ICAM‐1, VCAM‐1, and MMP‐9 were comparable between LT+/HCV+ and LT‐/HCV+ patients before eradication. HCV eradication decreased ICAM‐1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM‐1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT‐/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV‐ patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.

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Section: Discussionsupporting

confidence: 90%

HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation

et al. 2021

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“…The beneficial effect of tacrolimus may reflect the reduced incidence and degree of hypertension, hyperlipidemia, and/or renal injury compared to other immunosuppressants . It may be mechanistically plausible as cyclosporine has been shown to induce endothelial dysfunction and tacrolimus may have beneficial effects on endothelial function . The benefit of tacrolimus, however, was not notable compared to cyclosporine, which is more likely to be associated with many of the CV risk factors.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular disease after liver transplantation: When, What, and Who Is at Risk

et al. 2015

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The evolution of metabolic and cardiovascular disease (CVD) complications after liver transplantation (LT) is poorly characterized. We aim to illustrate the prevalence of obesity and metabolic syndrome (MS), define the cumulative incidence of CVD, and characterize risk factors associated with these comorbidities after LT. A retrospective review of 455 consecutive LT recipients from 1999 to 2004 with an 8-to 12-year follow-up was performed. Obesity increased from 23.8% (4 months) to 40.8% (3 years) after LT. Increase in body mass index predicted MS at 1 year after LT (odds ratio, 1.1; P < 0.001, per point). CVD developed in 10.6%, 20.7%, and 30.3% of recipients within 1, 5, and 8 years, respectively. Age, diabetes, hypertension, glomerular filtration rate < 60 mL/minute, prior CVD, ejection fraction < 60%, left ventricular hypertrophy, and serum troponin (TN) > 0.07 ng/mL were associated with CVD on univariate analysis. Age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06; P 5 0.019), diabetes (HR, 1.78; 95% CI, 1.09-2.92; P 5 0.022), prior history of CVD (HR, 2.46; 95% CI, 1.45-4.16; P < 0.001), and serum TN > 0.07 ng/mL (HR, 1.98; 95% CI, 1.23-3.18; P 5 0.005) were independently associated with CVD in the long term. Smoking history (ever), sex, hyperlipidemia, and serum ferritin levels were not predictive of CVD. Tacrolimus use versus noncalcineurin-based immunosuppression (HR, 0.26; 95% CI, 0.14-0.49; P < 0.001) was associated with reduced risk of CVD but not versus cyclosporine (HR, 0.67; 95% CI, 0.30-1.49; P 5 0.322). CVD is common after LT. Independent of MS, more data are needed to identify nonconventional risk factors and biomarkers like serum TN. Curbing weight gain in the early months after transplant may impact MS and subsequent CVD in the long term. Liver Transpl 21:889-896, 2015. V C 2015 AASLD.Received December 31, 2014; accepted March 22, 2015. See Editorial on Page 870Patient selection for liver transplantation (LT) is a multifaceted process aimed at identifying those at highest risk of poor outcomes. Many patients are excluded as candidates because of severe metabolic syndrome (MS) or cardiovascular disease (CVD). Despite exclusion of these individuals, LT recipients remain at high risk for development of CVD, but the risk is poorly characterized. Obesity and MS are more common in LT recipients than in the general

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“…While no uniform guidelines are currently available in the pre-LT assessment for CVD and every center adopts different routines, the consideration of CVD as a valid post-LT endpoint remains challenging. [69][70][71][72][73] Disease Recurrence and De Novo Malignancy Disease recurrence after LT can relate to recurrence of a malignant, viral, autoimmune or lifestyle disease 17 (Table S1, SDC, http://links.lww.com/TP/C302). In light of the ongoing organ scarcity, recurrence as modifiable clinical endpoint and selection criteria for patients undergoing LT for oncological disease were established.…”

Section: Morbidity Complication Rate Renal Function and Cardiovascula...mentioning

confidence: 99%

Section: The Value Of Current Endpoints In Liver Transplantation Studiesmentioning

confidence: 99%

The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation

et al. 2021

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Liver transplantation (LT) survival rates have continued to improve over the last decades, mostly due to the reduction of mortality early after transplantation. The advancement is facilitating a liberalization of access to LT, with more patients with higher risk profiles being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of high-risk donors. This is facilitated by novel technologies such as machine perfusion. Owing to these developments, reconsideration of the current and emerging endpoints for the assessment of the efficacy of existing and new therapies is warranted. While conventional early endpoints in LT have focused on the damage induced to the parenchyma, the fate of the bile duct and the recurrence of the underlying disease have a stronger impact on the long-term outcome. In light of this evolving landscape, we here attempt to reflect on the appropriateness of the currently used endpoints in the field of LT trials.

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Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Cited by 8 publications

References 22 publications

HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation

HCV eradication in recurrent hepatitis C after liver transplantation normalizes enhanced endothelial activation

Cardiovascular disease after liver transplantation: When, What, and Who Is at Risk

The Need to Update Endpoints and Outcome Analysis in the Rapidly Changing Field of Liver Transplantation

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