Pharmacological Inhibition of Vanin Activity Attenuates Transplant Vasculopathy in Rat Aortic Allografts

Wedel, Johannes; Jansen, Patrick A.; Botman, Peter N. M.; Rutjes, Floris P. J. T.; Schalkwijk, Joost; Hillebrands, Jan-Luuk

doi:10.1097/tp.0000000000001169

Cited by 12 publications

(5 citation statements)

References 40 publications

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“…Schalkwijk and coworkers developed a pantetheine analog, RR6, which showed high specificity towards vanin 1 [90]. The compound competitively and reversibly inhibited pantetheinase activity at nanomolar concentration; its potency was also confirmed in in vivo rat models [33,49,91]. Though further in-depth studies are warranted to specify the relevance of vanin 1 inhibition, compound RR6 certainly forms an exciting starting point to advance our knowledge of vanin biology and may lead to new therapeutic anti-inflammatory strategies.…”

Section: Discussionmentioning

confidence: 99%

Vanin 1: Its Physiological Function and Role in Diseases

Bartucci

Salvati

Olinga

et al. 2019

IJMS

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The enzyme vascular non-inflammatory molecule-1 (vanin 1) is highly expressed at gene and protein level in many organs, such as the liver, intestine, and kidney. Its major function is related to its pantetheinase activity; vanin 1 breaks down pantetheine in cysteamine and pantothenic acid, a precursor of coenzyme A. Indeed, its physiological role seems strictly related to coenzyme A metabolism, lipid metabolism, and energy production. In recent years, many studies have elucidated the role of vanin 1 under physiological conditions in relation to oxidative stress and inflammation. Vanin’s enzymatic activity was found to be of key importance in certain diseases, either for its protective effect or as a sensitizer, depending on the diseased organ. In this review, we discuss the role of vanin 1 in the liver, kidney, intestine, and lung under physiological as well as pathophysiological conditions. Thus, we provide a more complete understanding and overview of its complex function and contribution to some specific pathologies.

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Section: Discussionmentioning

confidence: 99%

Vanin 1: Its Physiological Function and Role in Diseases

Bartucci

Salvati

Olinga

et al. 2019

IJMS

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“…In this study, we showed the role of vanin-1 in the induction of tubular damage and subsequent renal fibrosis using rats with UUO. However, a causal association should be established by the use of pharmacological inhibitors of vanin-1 [ 29 ] or genetic models. In conclusion, vanin-1 that was released in the renal pelvic urine was detected in the UUO rats.…”

Section: Discussionmentioning

confidence: 99%

Vanin-1 in Renal Pelvic Urine Reflects Kidney Injury in a Rat Model of Hydronephrosis

Hosohata

Jin

Iwanaga

2018

IJMS

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Urinary tract obstruction and the subsequent development of hydronephrosis can cause kidney injuries, which results in chronic kidney disease. Although it is important to detect kidney injuries at an early stage, new biomarkers of hydronephrosis have not been identified. In this study, we examined whether vanin-1 could be a potential biomarker for hydronephrosis. Male Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO). On day 7 after UUO, when the histopathological renal tubular injuries became obvious, the vanin-1 level in the renal pelvic urine was significantly higher than that in voided urine from sham-operated rats. Furthermore, vanin-1 remained at the same level until day 14. There was no significant difference in the serum vanin-1 level between sham-operated rats and rats with UUO. In the kidney tissue, the mRNA and protein expressions of vanin-1 significantly decreased, whereas there was increased expression of transforming growth factor (TGF)-β1 and Snail-1, which plays a pivotal role in the pathogenesis of renal fibrosis via epithelial-to-mesenchymal transition (EMT). These results suggest that vanin-1 in the renal pelvic urine is released from the renal tubular cells of UUO rats and reflects renal tubular injuries at an early stage. Urinary vanin-1 may serve as a candidate biomarker of renal tubular injury due to hydronephrosis.

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“…NK cells may also play a role in damping chronic inflammatory responses by killing donor-derived tissue-resident CD4 T cells that provide help to host B cells that produce DSAs (37••). Graft-derived molecules including vanin (38) and N-octanoyl dopamine (39) may promote AV by enhancing macrophage vessel infiltration and apoptosis of SMCs, respectively.…”

Section: The Roles Of Innate Immune Cells In Avmentioning

confidence: 99%

Recent advances in allograft vasculopathy

Merola

Jane‐wit²,

Pober³

2017

Current Opinion in Organ Transplantation

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Purpose of review Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy (AV). This review discusses recently reported mechanistic insights of AV pathogenesis as well recent clinical evaluations of new therapeutic approaches. Recent findings Although adaptive immunity is the major driver of AV, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, NK cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4 T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of non-canonical NF-κB signaling. New clinical studies evaluating mTOR and proteasome inhibitors to target these pathways have been reported. Summary AV is a pathology resultant from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials.

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Pharmacological Inhibition of Vanin Activity Attenuates Transplant Vasculopathy in Rat Aortic Allografts

Cited by 12 publications

References 40 publications

Vanin 1: Its Physiological Function and Role in Diseases

Vanin 1: Its Physiological Function and Role in Diseases

Vanin-1 in Renal Pelvic Urine Reflects Kidney Injury in a Rat Model of Hydronephrosis

Recent advances in allograft vasculopathy

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