A Novel Liposome-Based Therapy to Reduce Complement-Mediated Injury in Revascularized Tissues

Goga, Ledia; Pushpakumar, Sathnur; Perez-Abadia, Gustavo; Olson, Paul; Anderson, Gary L.; Soni, Chirag; Barker, John H.; Maldonado, Claudio

doi:10.1016/j.jss.2010.09.033

Cited by 7 publications

(7 citation statements)

References 41 publications

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“…In our study, we used a warm ischemia of 45 min and this time constraint did not allow us to perform optimal incubation of FLVs and VCP as we did in highly successful cell based experiments. [52] We feel that our modest findings could have resulted from shorter duration of FLVs and VCP incubation, which led to reduced metal tether incorporation, and thus less VCP on the cell membranes. Our goal in future studies is to address this issue with better formulation of FLVs which will enable rapid incorporation of tethers with a shorter incubation period.…”

Section: Discussionmentioning

confidence: 99%

Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Pushpakumar¹,

Perez-Abadia²,

Soni³

et al. 2011

Journal of Surgical Research

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Background Excessive complement activation is an integral part of ischemia and reperfusion (IR) injury (IRI) of organs. In kidney transplantation the pathological consequence of IRI and complement activation can lead to delayed graft function which in turn is associated with acute rejection. Previous strategies to reduce complement induced IRI required systemic administration of agents, which can lead to increased susceptibility to infections/immune diseases. The objective of this study was to determine whether an increase in complement control defenses of rat kidney endothelium reduces IRI. We hypothesized that increased complement control on the endothelial barrier reduces IR-mediated complement activation and reduces kidney dysfunction. Materials and methods Fisher 344 rats underwent left kidney ischemia for 45 min. and treatment with a novel fusogenic lipid vesicle (FLVs) delivery system to decorate endothelial cells with Vaccinia virus complement control protein (VCP), followed by reperfusion for 24h. Assessment included renal function by serum creatinine and urea, myeloperoxidase assay for neutrophil infiltration, histopathology, and quantification of C3 production in kidneys. Results Animals in which the kidney endothelium was bolstered by FLVs+VCP treatment had better renal function with a significant reduction in serum creatinine as compared to vehicle controls. C3 production was significantly reduced (p<0.05) in treated animals compared to vehicle controls. Conclusion Increasing complement control at the endothelial barrier with FLVs+VCP modulates complement activation/production during the first 24h, reducing renal dysfunction following IRI.

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Section: Discussionmentioning

confidence: 99%

Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Pushpakumar¹,

Perez-Abadia²,

Soni³

et al. 2011

Journal of Surgical Research

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“…Preparation of FLVs was performed as previously reported by Goga et al with a few minor modifications [19]. Briefly, 1,2-Dioleoyl-sn-glycerol-3-phosphocholine (DOPC), 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphate (DOPA), and/or 1,2-Dioleoyl- sn -Glycero-3-[N(5-Amino-1-Carboxypentyl)iminodiAcetic Acid]succinyl zinc salt (DOGS-NTA-Zn 2+ ) were mixed at the appropriate ratio.…”

Section: Methodsmentioning

confidence: 99%

“…Our group has focused on developing liposomal-based therapeutic strategies that protect against reperfusion injury by decorating the endothelial barrier of organs with protective agents during ex vivo preservation [19,20]. We have developed specially formulated fusogenic lipid vesicles (FLVs) that, when infused into organs intra-arterially, rapidly incorporate lipids into endothelial cell membranes, which appear to interfere with cell activation.…”

Section: Introductionmentioning

confidence: 99%

Stabilizing endothelium of donor hearts with fusogenic liposomes reduces myocardial injury and dysfunction

Fensterer

Keeling

Patibandla

et al. 2013

Journal of Surgical Research

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Background Myocardial injury after heart transplantation is a consequence of pathophysiological events initiated by local ischemia/reperfusion (IR) injury that is further aggravated by the inflammatory response due to blood exposure to the pump’s artificial surfaces during cardiopulmonary bypass (CPB). The purpose of this study was to determine the effectiveness of fusogenic lipid vesicles (FLVs) in enhancing the cardioprotective effect of St. Thomas organ preservation solution (ST). We hypothesized that donor hearts preserved with ST-FLVs will stabilize the endothelium during reperfusion, which in turn will reduce both endothelial barrier dysfunction and myocardial damage. Materials and methods To examine the effect of ST-FLVs therapy in vitro, C3b deposition and adhesion molecule expression studies were performed on human umbilical vein endothelial cells (HUVECs) challenged with plastic-contact-activated plasma. To assess the therapy in vivo, a cervical heterotopic working heart transplantation model in rats was used. Donor hearts were preserved for 1 h at 27°C (15min) and 4°C (45min), and after transplant were followed for 2 h. Left ventricular (LV) function and blood cardiac troponin I (cTnI) levels were quantified. Results HUVECs treated with ST-FLVs had reduced C3b deposition and expression of adhesion molecules compared to ST alone (P<0.05). Donor hearts receiving ST-FLVs therapy had reduced LV dysfunction and cTnI compared to ST alone Conclusion We conclude that FLVs enhance the cardioprotective effect of ST and reduce post-ischemic LV dysfunction and myocardial damage. The mechanism of protection appears to be associated with the stabilization of endothelial cell membranes due to incorporation of FLV-derived lipids.

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“…al., [10] produced a study decorating cells with SA-CVP: vaccinia virus complement control protein (VCP), a potent anti-complement protein on cell membrane to reduce complement activation and deposition, linked with Streptavidin (SA). The results were satisfactorywith reduced complement activation and deposition in vitro and potential for application against inappropriate complement activation in vivo [10].…”

Section: Novel Liposome-based Therapymentioning

confidence: 99%

Treatment of Post-Revascularization Syndrome: brief communication

Freitas¹,

Martins²,

Lima³

et al. 2015

Int Arch Med

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Post-Revascularization Syndrome (PRS), also described as, Ischemic Reperfusion Injury (IRI), is the main cause of failure in the revascularization of limbs. The etiology of Port-Revascularization Syndrome is not fully known, but it is accepted as a multifactorial chain with a time-dependent molecular and structural change of the affected tissues. Current clinical treatments of PRS are supportive only notwithstanding numerous intervention strategies have been proposed aiming at reducing IRI. The present perspective aimed to explain all the available treatments in studies of IRI, and their potential effects in the future medicine. Since there are almost no articles covering this topic, we believe that this perspective will clarify the necessity of more researchers and studies on IRI. Our main findings leads to believe that there are many possible therapies for ischemic reperfusion injury, but most of them are still not used in practical scenarios because of it small samples studies, or in vitro techniques or the clinical trials are still not concluded. Although, significant work remains to be done. Contact information:Modesto Leite Rolim Neto. modestorolim@yahoo.com.br KeywordsPost-Revascularization Syndrome; Treatment; Review.Post-Revascularization Syndrome (PRS), also described as, Ischemic Reperfusion Injury (IRI), is the main cause of failure in the revascularization of limbs and the transfer of free flaps with 'non reflow' phenomenon [1]. It involves microcirculatory collapse during revascularization following an ischemic insult, that constitutes an acute inflammatory process by which cells are damaged first by temporary ischemia, hypoxia and accumulation of toxic metabolites and later by reperfusion [2,3]. It may result from thrombotic occlusion, embolism, trauma or surgical intervention through tourniquet application and subsequent restoration of blood flow.

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A Novel Liposome-Based Therapy to Reduce Complement-Mediated Injury in Revascularized Tissues

Cited by 7 publications

References 41 publications

Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Stabilizing endothelium of donor hearts with fusogenic liposomes reduces myocardial injury and dysfunction

Treatment of Post-Revascularization Syndrome: brief communication

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