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In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy.

ABSTRACT: Cardiac allograft vasculopathy is a major cause of morbidity and mortality of cardiac transplant recipients. The underlying cause of this disease remains unclear. Histological studies have implicated accelerated hemostasis and intravascular fibrin deposition in its pathogenesis. In the present study a defined model of this disease in the rat was used to elucidate the implication of tissue factor in the production of the hypercoagulable state observed in cardiac allograft vessels. Tissue factor protein and mRNA expression were studied in rat heart allografts developing allograft vasculopathy resembling human disease. Immunohistochemistry demonstrated tissue-factor-positive cells present in the allograft coronary intima and adventitia. Significant staining for tissue factor was detected in the endothelium lining coronary lesions in cardiac allografts and in interstitial mononuclear cells, respectively. Both transplant coronary endothelial cells and mononuclear cells contained tissue factor mRNA as indicated by oligo-cell reverse transcription polymerase chain reaction after laser-assisted cell picking. In contrast, tissue factor mRNA and protein were not or negligibly detectable within the coronary intima of nontransplanted control hearts. Thus, the present study clearly demonstrates that aberrant tissue factor expression occurs within the coronary intima after cardiac transplantation. Tissue factor, activating downstream coagulation mechanisms, may account for the intravascular clotting abnormalities observed in cardiac allografts and may represent a key factor in transplant atherogenesis.

SUBMITTER: Holschermann H

PROVIDER: S-EPMC1853432 | biostudies-literature | 1999 Jan

REPOSITORIES: biostudies-literature

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In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy.

Hölschermann H H Bohle R M RM Zeller H H Schmidt H H Stahl U U Fink L L Grimm H H Tillmanns H H Haberbosch W W

The American journal of pathology 19990101 1

Cardiac allograft vasculopathy is a major cause of morbidity and mortality of cardiac transplant recipients. The underlying cause of this disease remains unclear. Histological studies have implicated accelerated hemostasis and intravascular fibrin deposition in its pathogenesis. In the present study a defined model of this disease in the rat was used to elucidate the implication of tissue factor in the production of the hypercoagulable state observed in cardiac allograft vessels. Tissue factor p ...[more]

PMID: 9916935

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Project description:ObjectiveWe aimed to evaluate the diagnostic accuracy (DA) of dual-source CT coronary angiography (DSCTCA) against invasive coronary angiography (ICA) in assessing stenotic cardiac allograft vasculopathy (CAV) in heart transplant (HTX) recipients.MethodsConsecutive HTX recipients(n = 38) on annual surveillance, underwent DSCTCA prior to ICA on a 192-detector 384-slice DSCT scanner. Cases were classified as no CAV (no stenosis), any CAV (any degree of stenosis) or significant CAV (>50% stenosis).ResultsMean age was 33.66 ± 11.45 years (M:F = 27:11, median time from HTX-23.5 months). Prevalence of any CAV on DSCTCA and ICA was 44.7%(n = 17) and 39.5%(n = 15), respectively and that of significant CAV was 21.1%(n = 8) and 15.8%(n = 6), respectively. 557 (96.7%) segments were interpretable on DSCTCA. Mean radiation dose was 4.24 ± 2.15 mSv. At patient-level, the sensitivity, specificity, positive-predictive value, negative-predictive value (NPV), and DA of DSCTCA for detection of any CAV and significant CAV were 100%, 91.3%, 88.2%, 100%, 94.73% and 100%, 94%, 75%, 100%, 95% respectively. The same on segment-based analysis were 96%, 97.6%, 80%, 99.6%, 97.5% and 100%, 99.6%,86.7%,100%, 99.6%, respectively. There was excellent agreement between the two modalities for detection of any CAV and significant CAV [κ = 0.892 and 0.826 (patient-level), 0.859 and 0.927 (segment-level)]. CAC score correlated significantly with the presence of any CAV on both modalities. A diagnosis of rejection on biopsy did not correlate with any/significant CAV on DSCTCA or ICA.ConclusionHigh sensitivity and NPV of DSCTCA in the evaluation of stenotic CAV suggests that it can be an accurate and non-invasive alternative to ICA for routine surveillance of HTX recipients.Advances in knowledgeDSCTCA detects the stenotic CAV non-invasively in transplant recipients with high sensitivity, specificity and NPV when compared with catheter coronary angiography, at lower radiation doses. There is excellent agreement between CT angiography and catheter coronary angiography for detection of any CAV and significant CAV. A diagnosis of rejection on biopsy does not correlate with any/significant CAV on CT angiography or catheter angiography.

Project description:BackgroundThe association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options.MethodsThis prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx).ResultsDuring the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added.ConclusionResults of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Dataset Information

In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy.

Publications

In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy.

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