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Biomedical subjects

V Lindner

Publications and source records attributed to V Lindner.

At least 91 records · Page 5Linked to original sources
PubMed1992

Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty.

Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for vascular smooth muscle cells (SMC) in vitro, but its activities in vivo remain largely undefined. We infused recombinant PDGF-BB (0.01-0.30 mg/kg per d i.v.) into rats subjected to carotid injury. PDGF-BB produced a small increase (two- to threefold) in medial SMC proliferation. More importantly, PDGF-BB greatly increased (20-fold) the intimal thickening and the migration of SMC from the media to the intima during the first 7 d after injury. These data provide support for the hypothesis that PDGF, and perhaps other platelet factors, might play an important role in the movement of mesenchymal cells into zones of injury undergoing repair.

Angioplasty, Balloon↗
PubMed1992

Inhibition of smooth muscle cell proliferation in injured rat arteries. Interaction of heparin with basic fibroblast growth factor.

Heparin inhibits smooth muscle cell (SMC) proliferation after arterial injury by mechanisms that have yet to be defined. Since the initiation of SMC proliferation is mediated by basic fibroblast growth factor (bFGF), we have investigated the possibility that heparin inhibits SMC proliferation by displacing bFGF from the arterial wall. Using a rat carotid artery model of balloon catheter injury, we demonstrate that a bolus injection of heparin depletes the arterial wall of both systemically administered bFGF and of endogenous bFGF. Heparin, however, does not reduce the bFGF content of unmanipulated arteries. Further, a single injection of heparin given at the time of balloon injury reduces SMC proliferation by 55% but has no effect when given 6 h after injury. SMC proliferation induced in a denuded artery by injection of bFGF is inhibited almost completely by a bolus injection of heparin; however, pretreatment with a bolus of heparin does not prevent SMC from responding to a subsequent bolus of bFGF. These experiments suggest that heparin can inhibit SMC proliferation in part by removal of released bFGF from sites of injury.

Animals↗
PubMed1992

Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis.

Mesangial injury and cell proliferation are frequent findings in various glomerular diseases in man. Previous studies have demonstrated that basic fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5, and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the culture medium after antibody- and complement-mediated injury. Normal rat glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and 21.5 kD) could be demonstrated, which immunolocalized to the mesangium. Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after complement-mediated mesangiolysis. During the subsequent mesangial proliferative phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal infusion of heparin did not affect the bFGF immunostaining of glomeruli at this stage, indicating a predominantly intracellular localization of the bFGF. The capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further supported by experiments in which intravenous bFGF given 24 h after a subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase in glomerular cell proliferation (with > 60% of the cells identified as mesangial cells by double immunolabeling). No such increase was observed in normal rats injected with bFGF. These data show that mesangial cells produce and release bFGF after injury and that bFGF is mitogenic for injured mesangial cells in vivo. Release of mesangial cell bFGF thus may be an important mechanism involved in the initiation of mesangial cell proliferation in vivo.

Animals↗
PubMed1992

Factors controlling the development of arterial lesions after injury.

This review discusses the role of growth factors on the proliferation of smooth muscle cells (SMCs) in injured arteries. We have used a variety of procedures to injure rat carotid arteries and noted that removal of endothelium followed by platelet adherence does not always initiate SMC replication. Furthermore, thrombocytopenia did not reduce the early SMC replication induced by balloon catheter injury. Platelet-derived growth factor (PDGF) has been found to exert little effect on SMC replication but markedly influences the ability of SMCs to migrate to the intima. Basic fibroblast growth factor (bFGF) is a potent mitogen for SMCs in denuded arteries while having no effect on cells in control uninjured arteries. We have hypothesized that arterial injury leads to release of bFGF from injured SMCs and so stimulates cell replication. Rats were treated with antibodies to bFGF immediately before balloon injury, and this significantly reduced the SMC replication. These findings suggest that in vivo bFGF is an important mitogen for initiating SMC replication and that PDGF is important as a chemotactic for SMCs.

Animals↗
PubMed1992

Intimal smooth muscle cell proliferation after balloon catheter injury. The role of basic fibroblast growth factor.

The localization and synthesis of basic fibroblast growth factor (bFGF) in the rat carotid artery were investigated at times of chronic smooth muscle cell proliferation. Immunocytochemical staining showed the presence of bFGF in the uninjured arterial wall, and after balloon injury, this cellular staining was decreased. Western and northern blot analyses likewise showed that the amount of bFGF protein and mRNA decreased after injury. A neutralizing antibody to bFGF was administered 4 and 5 days after injury and was found to have no effect on intimal smooth muscle cell proliferation. These data suggest that an increase in the expression of bFGF is not necessary for chronic smooth muscle cell proliferation observed after balloon catheter injury and that bFGF is not the major mitogen responsible for intimal smooth muscle cell proliferation.

Animals↗
PubMed1991

Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor.

Proliferation of smooth muscle cells (SMCs) represents an important event in vascular lesion formation. Despite the common belief that growth factors contribute to the development of the atherosclerotic plaque, until now there has been no direct evidence for a role of mitogens in the development of arterial lesions. Balloon catheter injury of the rat carotid artery is accompanied by death of medial SMCs and is typically followed by proliferation of SMCs with subsequent formation of an intimal lesion. Our hypothesis is that injury causes mitogens to be released from dead cells, which then stimulate cell proliferation. One such mitogen that may be important in this process is basic fibroblast growth factor (bFGF), which can be detected immunocytochemically in SMCs and endothelial cells of adult rat carotid arteries. Systemic injection of a neutralizing antibody against bFGF prior to balloon catheterization significantly decreased the induced SMC proliferation by approximately 80%. The intimal lesion that developed within 8 days after injury, however, was not significantly reduced. The results of this study support the concept that endogenous bFGF is the major mitogen controlling the growth of vascular smooth muscle cells following injury. These data may have implications for the observed failure of endarterectomy and angioplasty procedures.

Animals↗
PubMed1991

Role of basic fibroblast growth factor in vascular lesion formation.

In the present study we investigated whether basic fibroblast growth factor (bFGF) plays a role in the proliferative response of smooth muscle cells (SMCs) to denuding injury. Rat carotid smooth muscle was found to express the mRNA for bFGF, and bFGF protein was found to be present in rat aorta by immunoblot analysis. Systemically administered bFGF was a potent mitogen for vascular SMCs in arteries denuded with a balloon catheter, increasing replication from 11.5% in controls to 54.8%. Denudation with a device (filament loop), which causes only minimal damage to medial SMCs, showed a similar increase in replication (1.3% versus 43.3%) after bFGF infusion. In unmanipulated vessels, however, SMCs were unresponsive to infused bFGF. Infusion of a "mitotoxin" (bFGF conjugated to saporin) caused a greater than 50% decrease in the number of viable SMCs in the arterial wall after balloon injury. Prolonged administration of bFGF (12 micrograms/day for 2 weeks) after balloon injury caused an approximately twofold increase in intimal thickening. These results show that bFGF, which is synthesized by the arterial wall, could be a potent mitogen for SMCs in vivo and suggest that any release of endogenous bFGF may be capable of stimulating SMC proliferation, which may subsequently lead to intimal lesion formation.

Animals↗
PubMed1991

Production of transforming growth factor beta 1 during repair of arterial injury.

Repair of arterial injury produced by balloon angioplasty leads to the formation of a neointima and a narrowing of the vascular lumen. In this study, we examined the possibility that smooth muscle cells (SMC) in injured rat carotid arteries are stimulated to produce type-1 transforming growth factor-beta (TGF-beta 1) during neointima formation in vivo. Levels of TGF-beta 1 transcripts (2.4 kb) were significantly increased within 6 h after carotid injury and reached a maximum (five to sevenfold) by 24 h. Regenerating left carotids had sustained increases in TGF-beta 1 mRNA levels (about fivefold) over the next 2 wk, during which time a substantial neointimal thickening was formed. No changes in basal TGF-beta 1 mRNA levels were found in contralateral uninjured carotids at any of the times examined. Immunohistochemical studies showed that a large majority of neointimal SMC were stained for TGF-beta 1 protein in an intracellular pattern, consistent with active TGF-beta 1 synthesis in this tissue. Neointima formation and TGF-beta 1 immunoreactivity were correlated with increases in fibronectin, collagen alpha 2(I), and collagen alpha 1(III) gene expression. Infusion of purified, recombinant TGF-beta 1 into rats with a preexisting neointima produced a significant stimulation of carotid neointimal SMC DNA synthesis. These results suggest that TGF-beta 1 plays an important role as an endogenous growth regulatory factor produced by neointimal SMC themselves during progressive neointimal thickening after balloon angioplasty.

Angioplasty, Balloon↗
PubMed1990

Early neurological abnormalities following coronary artery bypass surgery. A prospective study.

A prospective analysis of 78 patients undergoing coronary artery bypass surgery (CABS) was carried out to assess clinically the frequency and course of cerebral complications during the 1st postoperative week. Detailed evaluation of the patients showed that neurological abnormalities after CABS were common, occurring in 40 of the 78 patients (51%). However, there were no serious cerebral complications. Changes in reflexes and new focal signs were found in 26 and 25 cases respectively; in 7 patients (9%) they were confined to the first postoperative days. There was no statistically significant correlation between postoperative outcome and age, preoperative neurological state or bypass time. However, some strong associations could be calculated between a history of cerebrovascular signs or symptoms and the appearance of persisting focal signs or development reflexes during the 1st week after CABS.

Adult↗
PubMed1990

Changes in cerebral haemodynamics in cases of post-lumbar puncture headache: a prospective transcranial Doppler ultrasound study.

We used transcranial Doppler ultrasonography in 45 patients to investigate if changes in haemodynamics in the major arteries of the brain base occurred after lumbar puncture and whether or not patients with or without post-lumbar puncture headache differ with respect to their cerebral haemodynamic parameters before and after lumbar puncture. Before lumbar puncture, patients with post-lumbar puncture headache differed from patients without post-lumbar puncture headache in that they showed significantly higher flow velocities and significant asymmetry of flow velocities with lateralization to the right (p less than or equal to 0.05). Patients without post-lumbar puncture headache, on the other hand, showed non-significant flow velocity lateralization to the left. Forty-eight hours after lumbar puncture, both groups demonstrated symmetrical flow velocities. In addition, only patients with post-lumbar puncture headache showed a significant reduction in the flow velocity of the right middle cerebral artery (p less than or equal to 0.05). These findings suggest that it is not only absolute flow velocity that plays a part in the event of headache, the interhemispheric relation of cerebral haemodynamics also plays a fundamental role.

Adult↗
PubMed1990

[Hemodynamic reactions in the area supplied by the middle cerebral artery in post-puncture headache].

We used transcranial Doppler ultrasonography to investigate whether a change in hemodynamics in the major arteries of the brain base occurred after diagnostic lumbar puncture. On the day before diagnostic lumbar puncture the flow in the right and left middle cerebral artery was measured in 36 patients using transcranial Doppler ultrasonography. 48 hours after lumbar puncture a second ultrasound examination was performed. We found that only patients with post-lumbar puncture headache (PLPS) showed a significant reduction in the flow of the right middle cerebral artery (p less than or equal to .05). These findings support the puncture-hole-seepage theory as pathogenetic principle of PLPS.

Adult↗
PubMed1990

Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries.

A large percentage of vascular reconstructions, endarterectomies, and angioplasties fail postoperatively due to thrombosis and restenosis. Many of these failures are thought to result from an inability of the vascular endothelium to adequately regenerate and cover the denuded area. After balloon catheter denudation of the rat carotid artery, regrowth of endothelium ceases after approximately 6 wk, leaving a large area devoid of endothelium. Here we show that this cessation of reendothelialization can be overcome by the systemic administration of basic fibroblast growth factor (bFGF). Administration of 120 micrograms bFGF over an 8-h period caused a highly significant increase in the replication rate of endothelial cells at the leading edge of 38.5 vs. 2.1% in controls, and, when given over a longer period of time (12 micrograms daily for 12 d), resulted in a significant increase in the extent of endothelial outgrowth onto the denuded surface. Furthermore, total regrowth could be achieved within 10 wk after balloon catheter denudation when 12 micrograms bFGF was injected twice per week for a period of 8 wk. Endothelium in unmanipulated arteries responded to bFGF with a significant increase in replication, but no increase in endothelial cell density was observed in these arteries. These data demonstrate that bFGF can act as a potent mitogen for vascular endothelial cells in vivo, and add considerably to our understanding of the mechanism underlying endothelial repair after in vivo vascular injuries.

Animals↗
PubMed1989

Intimal thickenings of jugular veins after application of a stimulus known to be sclerogenic in arteries.

The present study examined the intimal reactions of rabbit jugular veins to a stimulus known to elicit arteriosclerotic alteration in the artery wall. Repeated transmural electrical stimulation was applied to external jugular veins of both normo- and hypercholesterolaemic rabbits. Endothelial permeability, as well as changes in intimal architecture, were investigated by electron microscopy. Initially, the veins responded to electrical stimulation with an increased transendothelial transport of horseradish peroxidase (40,000 daltons). After application of the stimulation program for 4 weeks, intimal fibrous thickening (33%), cellular fibrous proliferation (50%), and organized mural thrombi were observed. The fibrous thickening was characterized by an abundance of connective tissue matrix and paucity of subendothelial cells. The cellular fibrous proliferate predominantly consisted of myocytes with few interspersed monocytes/macrophages and granulocytes. It resembled intimal plaques induced in carotid arteries by the same method. However, the venous thickenings showed limited size and a more pronounced fibrous response when compared with the arteriosclerotic lesions. The morphological similarities between the observed venous intimal thickenings and the different types of phlebosclerotic manifestations described in the literature, especially intimal proliferations in vein grafts, render the model of electrical stimulation suitable for the elucidation of underlying pathogenic mechanisms.

Animals↗
PubMed1989

Regrowth of arterial endothelium. Denudation with minimal trauma leads to complete endothelial cell regrowth.

Endothelial regeneration in the rat carotid artery was investigated using two different techniques of denudation. With balloon catheter denudation, medial cell death occurred, and endothelial regrowth stopped after several weeks, leaving a large area devoid of endothelium. After denudation with a new technique that removed the endothelium without damaging the media complete endothelial regrowth was achieved. Acutely after this denudation, large platelet thrombi were present on the subendothelial surface of vessels denuded with the filament loop. In contrast, balloon catheter denuded arteries showed only a platelet monolayer on their luminal surface. Within the first few weeks after denudation with either technique the regenerating endothelial cells stained strongly for basic fibroblast growth factor. At later times when replication of endothelium had stopped, the balloon catheter denuded vessels did not stain with this antibody. After filament denudation endothelial cell replication remained high until regrowth was complete and intensive staining was observed in the regenerating endothelial cells at all times. No differences were seen in staining of smooth muscle cells for transforming growth factor-beta and fibronectin in either set of denuded vessels. Both groups showed transforming growth factor-beta to be located in the developing intima and especially on the apical surface of luminal smooth muscle cells. The surface of these luminal smooth muscle cells also stained with antibody to fibronectin. These data demonstrate that total regrowth of endothelium can occur over large denuded areas despite the presence of transforming growth factor-beta and fibronectin on these surfaces. Furthermore the ability of these endothelial cells to proliferate would appear to be dependent on the presence of basic fibroblast growth factor and on the severity of the trauma induced by denudation.

Animals↗
PubMed1987

Ca2+ influx in spontaneously hypertensive rats is sensitive to calcium antagonists.

Upon perfusion with a solution containing Ca2+, after Ca2+-free perfusion, aortic rings from spontaneously hypertensive rats (SHR) responded with a contraction. The contraction was usually transient. When verapamil or nifedipine were added prior to and during Ca2+ repletion, the force developed was reduced to 25% of that of uninhibited contraction. Aortas from normotensive rats did not show comparable properties. These findings demonstrate that calcium influx in aortic smooth muscle of SHR occurs mainly via voltage-dependent calcium channels.

Animals↗
PubMed1987

Does the xanthine-xanthine oxidase system alter contractile behaviour of vascular smooth muscle?

Since xanthine oxidase (XOD) preparations are usually applied as crystalline suspensions in ammonium sulphate solution, we studied separately the contractile responses of excised rabbit carotid arteries to the free radical generating system of xanthine-XOD and ammonium ions. Using dialyzed XOD (0.1-0.2 U/ml) the contractile pattern of the xanthine-XOD system was characterized by initial contraction followed by relaxation. Identical contractile behaviour was observed when xanthine was omitted from that system. These contractile responses were indistinguishable from those obtained with ammonium sulphate (10-20 mM). The threshold concentration of ammonium sulphate for inducing contraction was 1-2 mM. Both Ca++-free solution and verapamil only slightly inhibited the contractions produced by XOD and ammonium sulphate. No contractile effect was observed with dialyzed XOD. We conclude that the contractile effects of the xanthine-XOD system on vascular smooth muscle are due to simultaneously applied ammonium ions, and our findings emphasize the need for further purification of XOD preparations when investigating their effects on smooth muscle.

Ammonia↗
PubMed1984

The binding of Evans blue to collagen and elastin in elastic tissue.

The binding of Evans blue to collagen and elastin in rabbit aortic tissue and in bovine ligamentum nuchae was studied following circulation in vivo of the dye and incubation in vitro in Evans blue containing plasma, respectively. Using collagenase and elastase, the dye was liberated from both tissues corresponding to their different contents of collagen and elastin. Disc electrophoretic analysis of the liberated dye showed, that it migrated as free Evans blue indicating that the binding of the dye to the macromolecules was due to spatial interactions rather than to fixation at specific prosthetic groups. The capability of collagen and elastin to bind Evans blue was demonstrated with the isolated proteins; it was shown elastin had a higher affinity to the dye than collagen. Treatment of the blued tissue with hyaluronidase and Triton X-100 showed that binding to complex carbohydrates and dye accumulation in the aqueous intra- or extracellular space seems to be negligible.

Animals↗