Beruflich Dokumente
Kultur Dokumente
June 2018
done by SNAPGene Viewer (GSL Biotech LLC), Clustal Omega (EMBL-EBI) PC222.
and statistics with SPSS 25 (IBM) software.
Results: Intermediate results from 52 patients (39 AAAs/13 controls) Duplex Scan and Histologic Assessment of
revealed no significant differences in the expression of the investigated
SNPs within the two groups. The P values and frequencies of heterozy- Acute Renal Injury in a Kidney-Kidney
gote and rare homozygote between AAAs and controls in LRP1, DAB2IP, Crosstalk Swine Experimental Model
CDKN2BAS, SORT1, and IL6R were 0.270 (13%/3%); 0.454 (7%/0%); 0.670 Anna Paula W. Baptista-Sincos,1 Igor Rafael Sincos,2 Felipe Coelho,3
(28.2%/15.4%); 0.709 (41%/15.4%); 1.0 (3%/1%), respectively. For LPA no poly- Nelson Wolosker,2 Ricardo Aun,1 Vitoria P. de Paula,1 Oskar G.
morphism could be detected. There was no significant correlation Kaufmann4. 1Hospital Israelita Albert Einstein, Sao Paolo, Brazil;
between those SNPs with AAA risk. 2
University of Sao Paulo Medical School, Sao Paolo, Brazil; 3Hospital
Conclusions: For the preliminary data, there is no correlation between Vascular de Londrina, Londrina, Brazil; 4Federal University of São
polymorphism of the tested SNPs with AAA. Despite of this result, larger Paulo, Sao Paolo, Brazil
sample will lead to a new perspective.
Objectives: The objective of this study was to identify the effect of two
Author Disclosures: M. Herten: Nothing to disclose; N. T. Nugroho: left renal vasculature occlusion strategies on the duplex ultrasound-
Nothing to disclose; N. Osada: Nothing to disclose; S. Sielker: Nothing assessed rheology and histology of the contralateral kidney.
to disclose; G. Torsello: Nothing to disclose. Methods: Pigs were randomly assigned to one of two groups: left renal
artery-only clamping (A group, n ¼ 8) or left renal artery and vein clamp-
ing (AV group, n ¼ 9). Bilateral renal parenchymal biopsy specimens were
PC220. taken every 10 minutes for 90 minutes. Duplex ultrasound resistive index
(RI) and pulsatility index (PI) were measured. Mixed models with normal
distribution and first-order autoregressive correlation structure and
Impaired Wound Healing in Diabetes Is Driven by generalized estimating equation models were used. Results are pre-
Epigenetic Regulation of the Cyclo-Oxygenase-2/ sented as adjusted means with standard errors, estimated proportions
PGE2 Pathway in Macrophages with standard errors, and line plots with 95% confidence intervals.
Results: RI and PI increased in the nonischemic kidney (Figs 1 and 2). In
Frank M. Davis,1 Amrita Joshi,2 Andrew Kimball,1 Matthew Schaller,2
A group animals, RI values increased significantly (P < .01) after 30
Aaron denDekker,2 Bethany Moore,2 Katherine Gallagher1. 1Univer-
minutes of ischemia and PI increased significantly (P < .04) from 30 to
sity of Michigan Medical Center, Ann Arbor, Mich; 2University of
60 minutes of ischemia. The number of histologic abnormalities was
Michigan, Ann Arbor, Mich
higher in A group than in AV group biopsy specimens. The percentage
Objectives: Macrophage (M) plasticity, allowing for transition of Ms of lesions increased significantly after 10 minutes in A group nonischemic
from an inflammatory to a reparative phenotype, is critical for normal kidneys (P < .02) and between 50 and 80 minutes in AV group nonische-
wound healing. In pathologic conditions, such as type 2 diabetes mic kidneys (P < .01). Our finding that the nonischemic kidney experi-
(T2D), wounds fail to heal owing to impaired resolution of inflamma- enced acute effects stemming from contralateral ischemia may help
tion. The mechanism(s) responsible for the persistent inflammatory M surgeons prevent acute kidney injury during vascular and urologic
phenotype in T2D wounds are unclear. There is increasing evidence procedures. Moreover, simultaneous artery and vein clamping seemed
that epigenetic-based mechanisms control M function. These mecha- to affect the occurrence of renal crosstalk, which was reflected in wors-
nisms include DNA hypomethylation that leads to overexpression of ening perfusion, elevated resistive index and pulsatility index values,
genes. The cyclo-oxygenase (COX)-2/prostaglandin E2 (PGE2) axis as and a tendency for thrombi to form in control kidneys. In addition, renal
well as upstream pathways including cytosolic phospholipase (c(PL) clamping protocol affected the occurrence of histologic lesions.
A2), involved in the release arachidonic acid, have been associated Conclusions: The nonischemic kidney experienced acute effects stem-
with chronic inflammation, however these pathways have not been ming from contralateral ischemia, and the hilar clamping protocol
examined in diabetic wounds. The purpose of this study was to seemed to affect the occurrence of renal crosstalk, which was reflected
investigate if epigenetic modifications alter gene expression of the in worsening perfusion, elevated RI and PI values, and a tendency for
COX-2/PGE2 and c(PL)A2 pathway leading to derangements in M thrombi to form in nonischemic kidneys. The analysis of acute histologic
inflammation in diabetes. findings and Doppler ultrasound parameters indicated that RI and PI
Methods: Using our murine model of wound healing, wound Ms were measurements may have predictive value in AKI. We believe that intrao-
isolated from control and diet-induced obese (DIO) mice (n ¼ 40/group). perative Doppler ultrasound imaging can help to guide surgeons in
Expression of miR-29B, c(PL)A2, COX2, and PGE2 were determined by determining tolerable ischemia times and the probability of AKI onset.
qPCR. TGF protein was examined by ELISA. Standard phenotyping and Nevertheless, further clinical and experimental research is required to
killing assays were used to determine M function in DIO and control fully understand ischemia- reperfusion injury and renal crosstalk.
BMDM. Statistical significance was determined between two groups us-
ing Student t tests, and differences between more than two groups
were evaluated by analysis of variance followed by Newman-Keuls post
hoc test.
Results: We demonstrate that c(PL)A2 seems to be significantly upre-
gulated in diabetic Ms and human diabetic monocytes. In addition,
TGF is significantly elevated in DIO wound Ms in comparison to control
wound Ms. Further, the increase in TGF stimulates miR-29B production,
resulting in hypomethylation of the COX-2 gene and overexpression.
Increased COX-2 in diabetic Ms significantly increased PGE2 levels in
DIO wound Ms resulting inflammatory gene expression and impaired
killing/phagocytosis.
Conclusions: In summary, these results demonstrate that the COX-2/
PGE2 pathway is increased in diabetic wound Ms by elevated TGF/miR-
29b that hypomethylate COX-2 and results in elevated PGE2 that drives
M-mediated inflammation and impaired phagocytosis preventing
wound repair.