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At least 685 records · Page 38Linked to original sources
PubMed2000

Intravascular ultrasound imaging after cardiac transplantation: advantage of multi-vessel imaging.

BACKGROUND: Intravascular ultrasound is a sensitive tool to study transplant vasculopathy. However, there is no consensus regarding the methodology for imaging protocol. The impact of single versus multiple epicardial vessel imaging in determining the prevalence of transplant vasculopathy has not been determined. This study examines the benefit of three-vessel imaging versus one-vessel imaging in detecting transplant vasculopathy. METHODS AND RESULTS: One hundred eleven transplant recipients with intravascular ultrasound imaging at baseline (within 2 months of transplantation) were studied: 107 at 1-year, 53 at 2-year and 41 at 3-year follow-up. A total of 222 arteries, 519 segments and 772 sites were analyzed (94 LAD, 65 LCX and 65 RCA). The prevalence of transplant vasculopathy lesions was 27%, 41% and 58% at 1 year, 39%, 55% and 71% at 2 years and 39%, 55% and 74% at 3 years for patients with one-, two- and three-vessel imaging, respectively. Single- or two-vessel disease was present in 23% (7) and 32% (10) patients with three-vessel imaging, leading to the potential mislabeling of these 17 (55%) patients as "disease free" if they underwent only single-vessel imaging. CONCLUSIONS: Multivessel imaging is more sensitive in detecting the transplant vasculopathy lesions compared to single-vessel imaging. This important variable should be considered when designing and interpreting trials utilizing intravascular imaging derived end-point.

Adult↗
PubMed1995

Exogenous vascular endothelial growth factor induces malformed and hyperfused vessels during embryonic neovascularization.

Vascular endothelial growth factor (VEGF) is a potent and specific endothelial mitogen that is able to induce angiogenesis in vivo [Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V. & Ferrara, N. (1989) Science 246 1306-1309]. To determine if VEGF also influences the behavior of primordial endothelial cells, we used an in vivo vascular assay based on the de novo formation of vessels. Japanese quail embryos injected with nanomolar quantities of the 165-residue form of VEGF at the onset of vasculogenesis exhibited profoundly altered vessel development. In fact, the overall patterning of the vascular network was abnormal in all VEGF-injected embryos. The malformations were attributable to two specific endothelial cell activities: (i) inappropriate neovascularization in normally avascular areas and (ii) the unregulated, excessive fusion of vessels. In the first instance, supernumerary vessels directly linked the inflow channel of the heart to the aortic outflow channel. The second aberrant activity led to the formation of vessels with abnormally large lumens. Ultimately, unregulated vessel fusion generated massive vascular sacs that obliterated the identity of individual vessels. These observations show that exogenous VEGF has an impact on the behavior of primordial endothelial cells engaged in vasculogenesis, and they strongly suggest that endogenous VEGF is important in vascular patterning and regulation of vessel size (lumen formation).

Animals↗
PubMed2005

Modulation of nitric oxide synthase activity in brain, liver, and blood vessels of spontaneously hypertensive rats by ascorbic acid: protection from free radical injury.

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 +/- 7 mmHg and 142 +/- 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 +/- 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 +/- 0.02, 0.14 +/- 0.003, and 1.54 +/- 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 +/- 1%, 21 +/- 3%, and 44 +/- 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 +/-.03, 0.11 +/-.01, and 0.87 +/-.08 pmol citruline/mg protein to 0.93 +/- 0.01, 0.13 +/- 0.001, and 1.11 +/- 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 +/- 0.06, 0.11 +/- 0.005, and 0.47 +/- 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 +/- 3%, 64 +/- 3%, and 104 +/- 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 +/- 1% and 34 +/- 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 +/- 0.1%; p < 0.05), nitrite (53 +/- 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 +/- 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.

Animals↗
PubMed1995

Large blood vessel cooling in heated tissues: a numerical study.

Large blood vessels can produce steep temperature gradients in heated tissues leading to inadequate tissue temperatures during hyperthermia. This paper utilizes a finite difference scheme to solve the basic equations of heat transfer and fluid flow to model blood vessel cooling. Unlike previous formulations, heat transfer coefficients were not used to calculate heat transfer to large blood vessels. Instead, the conservation form of the finite difference equations implicitly modelled this process. Temperature profiles of heated tissues near thermally significant vessels were calculated. Microvascular heat transfer was modelled either as an effective conductivity or a heat sink. An increase in perfusion in both microvascular models results in a reduction of the cooling effects of large vessels. For equivalent perfusion values, the effective conductivity model predicted more effective heating of the blood and adjacent tissue. Furthermore, it was found that optimal vessel heating strategies depend on the microvascular heat transfer model adopted; localized deposition of heat near vessels could produce higher temperature profiles when microvascular heat transfer was modelled according to the bioheat transfer equation (BHTE) but not the effective thermal conductivity equation (ETCE). Reduction of the blood flow through thermally significant vessels was found to be the most effective way of reducing localized cooling.

Animals↗
PubMed2004

Photoacoustic determination of blood vessel diameter.

A double-ring sensor was applied in photoacoustic tomographic imaging of artificial blood vessels as well as blood vessels in a rabbit ear. The peak-to-peak time (tau(pp)) of the laser (1064 nm) induced pressure transient was used to estimate the axial vessel diameter. Comparison with the actual vessel diameter showed that the diameter could be approximated by 2ctau(pp), with c the speed of sound in blood. Using this relation, the lateral diameter could also precisely be determined. In vivo imaging and monitoring of changes in vessel diameters was feasible. Finally, acoustic time traces were recorded while flushing a vessel in the rabbit ear with saline, which proved that the main contribution to the laser-induced pressure transient is caused by blood inside the vessel and that the vessel wall gives only a minor contribution.

Acoustics↗
PubMed2006

Engineering of blood vessels from acellular collagen matrices coated with human endothelial cells.

Small-caliber synthetic grafts used for coronary bypass artery grafting are compromised by thrombogenicity and accelerated intimal thickening, resulting in early graft occlusion. Herein we describe the fabrication and physical properties of small-caliber blood vessels using decellularized porcine aortic segments. These vessels were further coated with human saphenous vein endothelial cells (HSVECs) for future clinical applications. Chemical staining of decellularized vessels showed that they preserved their native matrix architecture, including several collagen layers in between internal and external elastin layers. The burst pressure for the decellularized vessels was higher than 1,000 mmHg. HSVECs, seeded on the luminal side, adhered to the matrix and formed a uniform monolayer. HSVEC-seeded vessels produced prostaglandin I2 and released vasoactive agents in response to the calcium ionophore A23187. These results show that engineered blood vessels coated with the host endothelial cells possess morphologic and functional characteristics of human small-caliber vessels. Tissue-engineered vessels may potentially be useful clinically as vascular grafts.

Animals↗
PubMed1989

Alcohol use and retinal vessels: insights into the mechanism of alcohol-induced stroke.

Alcohol use is a recognized risk factor for stroke. We hypothesized that alcohol use may increase the risk of stroke, independent of an effect on blood pressure, by causing cerebral vasoconstriction. To examine this, we used retinal vessels as a marker for cerebral vessels and analysed the cross-sectional associations between alcohol use and total retinal vessel width in 741 Japanese and 434 American white male telephone executives. Systolic and diastolic blood pressures were negatively associated with retinal vessel width in the Japanese (p less than 0.0001, 0.0001, respectively) but this association did not achieve statistical significance in the Americans (p less than 0.1, 0.3). Japanese drinkers had a larger mean retinal vessel width than Japanese abstainers, while American drinkers had a smaller retinal vessel width than abstainers. These associations between alcohol use and retinal vessel width were not significant within nationalities but the interaction between alcohol use and nationality was significant, independent of other stroke risk factors (p less than 0.04). Although these results do not support the initial hypothesis, they are consistent with known biological differences in alcohol metabolism between Japanese and American men and support different effects of alcohol use on retinal vessel calibre in these two nationalities.

Adult↗
PubMedDate not supplied

In vitro studies on responses to noradrenaline, serotonin, and potassium of intramyocardial and mesenteric resistance vessels from Wistar rats.

We compared the responses to noradrenaline, serotonin, and potassium of isolated intramyocardial (flow-regulating) coronary and mesenteric resistance vessels of similar internal diameter (approximately 200 microns) from Wistar rats. The coronary but not the mesenteric resistance vessels had spontaneous basal tone, which was reduced by elimination of extracellular calcium, by increasing the extracellular potassium concentration up to 22 mM, and by stimulation of coronary vessels with noradrenaline. Noradrenaline always caused contraction of mesenteric resistance vessels and in coronary vessels after incubation with propranolol (3 X 10(-6) M). The noradrenaline and potassium concentration-response characteristics of the mesenteric resistance vessels were modulated by perivascular adrenergic nerve terminals, whereas no influence of nerve terminals could be shown in the coronary resistance vessels. The sensitivity of mesenteric vascular smooth muscle to noradrenaline [concentration required to give half maximal response (EC50) approximately 0.4 X 10(-6) M] and serotonin (EC50 approximately 0.3 X 10(-6) M) was higher (p less than 0.001) than the sensitivity of coronary smooth muscle (EC50 values 1.6 X 10(-6) and 1.3 X 10(-6) M, respectively). The potassium sensitivity of the coronary smooth muscle (EC50 approximately 35 mM) was higher than that of the mesenteric smooth muscle (EC50 approximately 41 mM; p less than 0.01). The respective maximal noradrenaline and serotonin responses relative to the maximal potassium response were 35 and 55% in the coronary and 127 and 120% in the mesenteric resistance vessels (p less than 0.001).

Animals↗
PubMed2003

Sensitivity, specificity and accuracy of stress SPECT myocardial perfusion imaging for detection of coronary artery disease in the distribution of first-order branch vessels, using an anatomical matching of angiographic and perfusion data.

We sought to investigate the utility of stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the identification of coronary artery disease (CAD) in the distribution of first-order branch vessels. We evaluated 135 consecutive patients with coronary angiography and stress SPECT MPI. We anatomically matched angiography and SPECT to assess the sensitivity, specificity and accuracy of SPECT MPI for the detection of CAD in the distribution of first-order branches. Subgroup analysis for stress test performance and previous coronary artery bypass grafting (CABG) was also performed. The sensitivity, specificity and accuracy of stress SPECT MPI for the detection of CAD in the distribution of first-order branch vessels were all 67%. For isolated branch vessel CAD, stress SPECT MPI had a sensitivity of 44%. In patients without CABG, the sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order branch vessels were 71%, 67% and 68%, compared with 60%, 67% and 64% for patients with CABG. The sensitivity for isolated branch vessel CAD was 50% for patients without CABG, but only 29% for patients with CABG. The sensitivity and specificity for CAD in the distribution of branch vessels were similar for all patients for all stress test modalities and heart rate response (sensitivity, 64-69%; specificity, 61-69%). Stress SPECT MPI offers intermediate sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order coronary artery branch vessels. However, for isolated branch vessel CAD, stress SPECT has a lower sensitivity, particularly in patients with previous CABG.

Coronary Angiography↗
PubMed2004

Location of vessel occlusion of calibrated tris-acryl gelatin microspheres for tumor and arteriovenous malformation embolization.

PURPOSE: To evaluate (i). the presence and number of calibrated tris-acryl gelatin microspheres (TGMS) in targeted organs after embolization of tumors or arteriovenous malformations (AVMs) and (ii). the possible correlations among the size of TGMS used for embolization, the size of TGMS found in specimens, and the size of the occluded vessels. MATERIALS AND METHODS: Histologic slides were reviewed of 92 specimens from 80 patients with primarily head and neck tumors or AVMs operatively treated after embolization with TGMS of various sizes (40-120 microm, 100-300 microm, 300-500 microm, 500-700 microm, 700-900 microm, and 900-1200 microm). The diameters of the vessels containing TGMS, the size of TGMS, and the thickness of the inflammatory reactions developed around them were measured, and the location of the microspheres was recorded. RESULTS: TGMS were found in 88% of the specimens; 1985 embolized vessels containing TGMS were analyzed. The median number of TGMS per vessel was one (mean +/- SD, 3.1 +/- 6.9). The diameter of the occluded vessels increased significantly (P <.0001) with increased size of TGMS used for embolization. In tumors, 92% of the occluded vessels were located inside the tumor. CONCLUSION: There is an obvious correspondence between the size of the TGMS used for embolization and the diameter of the occluded vessels. This correlation confirms the possibility that the vessels to be occluded can be precisely targeted with the use of a proper TGMS size range.

Angiography↗
PubMed2000

Gray-scale skeletonization of small vessels in magnetic resonance angiography.

Interpretation of magnetic resonance angiography (MRA) is problematic due to complexities of vascular shape and to artifacts such as the partial volume effect. We present new methods to assist in the interpretation of MRA. These include methods for detection of vessel paths and for determination of branching patterns of vascular trees. They are based on the ordered region growing (ORG) algorithm that represents the image as an acyclic graph, which can be reduced to a skeleton by specifying vessel endpoints or by a pruning process. Ambiguities in the vessel branching due to vessel overlap are effectively resolved by heuristic methods that incorporate a priori knowledge of bifurcation spacing. Vessel paths are detected at interactive speeds on a 500-MHz processor using vessel endpoints. These methods apply best to smaller vessels where the image intensity peaks at the center of the lumen which, for the abdominal MRA, includes vessels whose diameter is less than 1 cm.

Algorithms↗
PubMed2003

Histological characteristics of tumors in blood vessels play an important role in tumor progression of invasive ductal carcinoma of the breast.

Whether the characteristics of tumor cells in blood vessels play an important role in the tumor progression of invasive ductal carcinoma (IDC) of the breast is not known. The purpose of this study was to investigate the significance of the characteristics of tumor cells in blood vessels in relation to tumor progression in 247 IDC patients with blood vessel invasion, in comparison with well-known histological parameters. Blood vessel tumor embolus dimensions were measured. Nuclear atypia, numbers of mitotic and apoptotic figures, and fibrosis grade of tumor cells in blood vessels were assessed. Cox proportional hazard multivariate analyses showed that >2 mitotic figures in blood vessel tumors significantly increased the hazard rates (HRs) of disease-free survival (P=0.002) and initial distant organ metastasis-free survival (IDOMS) in node-negative IDCs (P=0.005), and the HRs of disease-free survival (DFS, P=0.007) and IDOMS (P=0.015) in node-positive IDCs. Apoptotic figures >2 in blood vessel tumor emboli significantly increased the HR of overall survival (P=0.007) in node-positive IDCs. The present study showed the number of mitotic and apoptotic figures in tumor cells in the blood vessels to play a very important role in the tumor progression of IDCs.

Adult↗
PubMedDate not supplied

A review of sonographic identification of abdominal blood vessels and juxtavascular organs.

Abdominal vasculature can be evaluated non-invasively using 2-D ultrasound imaging and Doppler ultrasonography. The identification of abdominal vessels using ultrasound is based on knowledge of their normal location, appearance and relationship to specific organs. Because anatomic location of major abdominal vessels is fairly consistent, finding and following vessels is a useful aid when attempting to locate and evaluate juxta-vascular organs. Sonographic vascular evaluation may be beneficial in providing information regarding central cardiovascular abnormalities, detection of abnormalities involving the vessel interrogated, or detection of abnormalities of the parenchymal bed that the vessel supplies. Knowledge of the location and appearance of the vessels is necessary for this information to be of diagnostic value. In this paper, abdominal vessels in the dog are reviewed and a sonographic map of major abdominal vessels is described. This includes the sonographic appearance of the aorta, caudal vena cava, and protal vein, their major branches and their anatomic relationship with adjacent organs. Identification of the medial iliac lymph nodes, mesenteric lymph nodes, abdominal esophagus, duodenum, spleen, kidneys, pancreas, adrenal glands and liver lobes are assisted by recognizing specific vascular landmarks. The locations and appearances of pertinent organs as pertains to abdominal vasculature (caudal vena cava and aorta) are described.

Abdomen↗
PubMed1998

Morphogenesis of the first blood vessels.

The initial phase of vessel formation is the establishment of nascent endothelial tubes from mesodermal precursor cells. Development of the vascular epithelium is examined using the transcription factor TAL1 as a marker of endothelial precursor cells (angioblasts), and a functional assay based on intact, whole-mounted quail embryos. Experimental studies examining the role(s) of integrins and vascular endothelial growth factor (VEGF) establish that integrin-mediated cell adhesion is necessary for normal endothelial tube formation and that stimulation of embryonic endothelial cells with exogenous VEGF results in a massive "fusion" of vessels and the obliteration of normally avascular zones. The second phase of vessel morphogenesis is assembly of the vessel wall. To understand the process by which mesenchyme gives rise to vascular smooth muscle, a novel monoclonal antibody, 1E12, that recognizes smooth muscle precursor cells was used. Additionally, development of the vessel wall was examined using the expression fo extracellular matrix proteins as markers. Comparison of labeling patterns of 1E12 and the extracellular matrix molecules fibulin-1 and fibrillin-2 indicate vessel wall heterogeneity at the earliest stages of development; thus smooth muscle cell diversity is manifested during the differentiation and assembly of the vessel wall. From these studies it is postulated that the extracellular matrix composition of the vessel wall may prove to be the best marker of smooth muscle diversity. The data are discussed in the context of recent work by others, especially provocative new studies suggesting an endothelial origin for vascular smooth muscle cells. Also discussed is recent work that provides clues to the mechanism of vascular smooth muscle induction and recruitment. Based on these findings, vascular smooth muscle cells can be thought of as existing along a continuum of phenotypes. This spectrum varies from mainly matrix-producing cells to primarily contractile cells; thus no one cell type typifies vascular smooth muscle. This view of the smooth muscle cell is considered in terms of a contrasting opinion that views smooth muscle cell as existing in either a synthetic or proliferative state.

Animals↗
PubMed1980

Electron microscopical studies of vessels in diabetic peripheral neuropathy.

the results of an electron microscopical study of sural nerve biopsies from 11 patients with diabetic neuropathy are presented. Thrombi were seen in six cases in at least one intraneural vessel; nine cases showed hyperplasia of endothelial cells, and in seven out of these nine the hyperplasia was sufficient to occlude completely the lumen of small vessels; six cases showed degenerate pericytes and endothelial cells, and in some cases endothelial cells had been shed from the vessel wall, exposing the blood within the vessel to the underlying basement membrane; in five cases large lipid droplets were seen within endothelial cells. Abnormalities of the vessel wall would result in decreased fibrinolytic activity and a reduction of the antiplatelet aggregating proprties of the vessel. Desquamation of endothelial cells from the vessel wall, with exposure of platelets to underlying collagen, may act as a trigger for thrombus formation, particularly as the blood of diabetic patients is often in a hypercoagulable state. The significance of hyperplasia of endothelial cells is at present unknown but, once established, this too would result in profound alterations of loal blood flow and ischaemia of nerve. Damage to endothelial cells may also allow seepage of haematological constituents into the vessel wall, resulting in its progressive thickening.

Adult↗
PubMed1987

Use of ultrasound for noninvasive study of blood vessel responsiveness.

To provide a noninvasive means for studying individual macroscopic blood vessels, an ultrasound scanner was modified to provide a recording of blood vessel diameter. The instrument has A- and B-modes of signal display. The B-mode is used to position the probe and the A-mode to measure vessel diameter. The A-mode has two electronic gates for tracking the echo from each of two structures, i.e., near and far wall of vessel. The front gate was modified to pick up the falling rather than rising edge of a peak generated by the vessel wall. An analog signal proportional to the distance between gates was derived for recording with a strip-chart recorder. Probe holders were constructed to optimize positioning and holding of probe. Stability was excellent (reading varied 0.05 mm over 1 h). Axial resolution was between 0.3 and 0.73 mm. Discrepancy of measurements of plastic tubing made by ocular and ultrasound varied from 1.1 to 4.6%. Discrepancy with lightly fixed vessels was 2.7-8.2%. Ex vivo measurements on vessels with viable smooth muscle were more variable, perhaps because of actual change during measurements. Changes in vessel diameter induced by change in hydrostatic pressure and exposure to histamine were recorded.

Animals↗
PubMed1997

Response of native and stimulated collateral vessels to serotonin.

Previous studies suggest that collateral vessels constrict in response to serotonin. The objective of these studies was to directly measure responses of native and stimulated collateral vessels 30-400 microns in diameter to serotonin and to determine the mechanisms involved in responses to serotonin. Serotonin was suffused onto the left ventricle of dogs, and microvascular diameters were measured with computer-controlled stroboscopic illumination coupled to a microscope-video system. Stimulated collateral vessels and arterioles in collateral-dependent myocardium were measured after Ameroid constriction of the left circumflex artery. Noncollateral and native collateral vessels were examined in dogs without a constrictor. Serotonin produced dose-dependent dilation of noncollateral vessels that was decreased in native collateral vessels, stimulated collateral vessels, and vessels in collateral-dependent myocardium. Dilation in response to nitroprusside was similar in all groups. Dilation in response to serotonin was enhanced by inhibition of 5-hydroxytryptamine (5-HT)2 receptors with ketanserin and blocked by nonselective 5-HT1 and 5-HT2 receptors with methiothepin. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine decreased dilation in response to serotonin. Thus collaterals and arterioles in collateral-dependent myocardium are less sensitive to the dilating effect of serotonin. Responses to serotonin involve a balance between dilation mediated by 5-HT1 receptors and constriction mediated by 5-HT2 receptors.

Animals↗
PubMed2000

Expression, localization, and activity of tissue factor pathway inhibitor in normal and atherosclerotic human vessels.

Tissue factor (TF) pathway inhibitor (TFPI) is the major downregulator of the procoagulant activity of the TF-factor VIIa (FVIIa) complex (TF. FVII). The active TF present in the atherosclerotic vessel wall is proposed to be responsible for the major complication of primary atherosclerosis, namely, acute thrombosis after plaque rupture, but our knowledge of the sites of TFPI expression in relation to TF remains fragmentary. The aim of this study was to investigate the expression, localization, and activity of TFPI and its relation to the activity and distribution of TF in the normal and atherosclerotic vessel wall. We applied a novel approach in which serial cross sections of human vascular segments were used to perform a complete set of assays: immunolabeling for TFPI and/or TF, in situ hybridization for the expression of TFPI mRNA, ELISA for the determination of TFPI antigen, and functional assay for the activity of TFPI and TF. In healthy vessels, TFPI protein and mRNA are present in luminal and microvascular endothelial cells (ECs) and in the medial smooth muscle cells (SMCs). In atherosclerotic vessels, TFPI protein and mRNA frequently colocalized with TF in ECs overlying the plaque and in microvessels, as well as in the medial and neointimal SMCs, and in macrophages and T cells in areas surrounding the necrotic core. At the ultrastructural level, immunogold electron microscopy confirmed the localization of TFPI in ECs, macrophages/foam cells, and SMCs. In ECs and SMCs, the gold particles decorated the plasmalemma proper and the caveolae. ELISA on cross sections revealed that atherosclerotic tissues contain more TFPI than do the healthy vessels. TFPI was functionally active against TF. FVIIa-induced coagulation, and its activity was higher in those tissues that display less TF. The largest amount of TFPI and TF were detected in complicated arterial plaques. By immunofluorescence, TFPI colocalized with platelet- and fibrin-rich areas within the organized thrombi. Atherosclerotic vessel sections promote activation of factor X, which is dependent on the presence of TF and enhanced by preincubation of the sections with anti-TFPI IgG. Taken altogether, our results suggest that TFPI is largely expressed in the normal vessel wall and enhanced in the atherosclerotic vessel, in a manner suggesting a significant role of TFPI in the regulation of TF activity.

Arteriosclerosis↗