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PubMed2001

Plasma fibrinogen in relation to the severity of arteriosclerosis in patients with stable angina pectoris after myocardial infarction.

BACKGROUND: Authors both of retrospective and of prospective studies have demonstrated that there is a relationship between concentration of fibrinogen in plasma and the angiographically determined severity of coronary heart disease (CHD). OBJECTIVE: To determine the relevance of the plasma fibrinogen concentration for the severity of CHD, particularly in cases with additional arteriosclerotic changes in the extracranial arteries supplying the brain [cerebrovascular disease (CVD)], in the pelvic/leg arteries [peripheral occlusive arterial disease (POAD)], or in both. PATIENTS AND METHODS: In a retrospective cross-sectional survey the cardiological and angiographical status of a total of 1112 male and 299 female patients with stable angina pectoris after sustained myocardial infarction and an age-matched control group of 326 male and 138 female subjects with no clinical symptoms of CHD was determined, together with measurements of plasma fibrinogen, dynamic plasma viscosity and D-dimers. RESULTS: More than two-thirds of the patients with arteriosclerosis had plasma fibrinogen concentrations in the uppermost tertile of the control range (men > 2.75; women > 2.83 g/l). Plasma fibrinogen concentration was correlated to the severity of CHD (for men r = 0.173, P < 0.001; for women r= 0.144, P < 0.013). Patients with generalized arteriosclerosis had higher plasma fibrinogen concentrations than did those suffering from CHD only (for men, control 2.65 +/- 0.51, CHD 3.07 +/- 0.73, CHD plus POAD 3.17 +/- 0.77 and CHD plus POAD plus CVD 3.45 +/- 0.78 g/l; for women, control 2.69 +/- 0.44, CHD 3.25 +/- 0.67, CHD plus POAD 3.19 +/- 0.77, CHD plus POAD plus CVD 3.60 +/- 0.84 g/l). Multivariate analysis showed that C-reactive protein, D-dimers and dynamic plasma viscosity accounted for 48.2% (for men) and 49.4% (for women) of the variance in plasma fibrinogen concentration. CONCLUSIONS: Our findings demonstrate that there is not only a correlation between plasma fibrinogen concentration and the severity of CHD, but also a correlation to the incidence of additional POAD or CVD.

Adult↗
PubMed2005

Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis.

This study compared the effects of long-term administration of nicorandil and isosorbide dinitrate (ISDN) on vascular endothelial function and the progression of arteriosclerosis. Forty-two patients with ischemic heart disease were randomly allocated to receive nicorandil (N group; 15 mg/d) or ISDN (I group, 40 mg/d). Twelve normal subjects served as controls. Vascular endothelial function and the progression of arteriosclerosis (intima-media thickness, IMT), as determined by carotid vascular ultrasound, were assessed 1 week before and 3 months after drug administration. Reactive hyperemia was induced in the forearm for 5 minutes, and the percentage change in the diameter of the brachial artery (% change in flow-mediated dilation, %FMD) was calculated. FMD was significantly lower in CAD groups than in controls. The %FMD significantly decreased (7.2 +/- 1.9 to 4.2 +/- 2.8) in the I group, while rising from 6.8 +/- 1.6 to 8.0 +/- 2.0 in the N group. IMT increased by 0.036 +/- 0.015 mm in the I group but showed no significant change in the N group (-0.01 +/- 0.012 mm). Thus, ISDN deteriorates IMT and FMD, whereas a beneficial effect of nicorandil is seen on FMD with no effect on IMT. Long-term treatment with nicorandil may be desirable for prevention of cardiovascular events.

Administration, Oral↗
PubMed2004

Effects of AGI-1096, a novel antioxidant compound with anti-inflammatory and antiproliferative properties, on rodent allograft arteriosclerosis.

BACKGROUND: AGI-1096 is a novel phenolic intracellular antioxidant with anti-inflammatory and antiproliferative properties. In vitro, AGI-1096 inhibited the inducible expression of vascular cell adhesion molecule (VCAM)-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 in endothelial cells and tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells. It also inhibited serum-stimulated proliferation of aortic smooth-muscle cells. In vivo, AGI-1096 demonstrated anti-inflammatory properties in a murine delayed-type hypersensitivity model. Given these antioxidant, anti-inflammatory and antiproliferative properties, we reasoned that AGI-1096 may be able to prevent chronic allograft arteriosclerosis. This hypothesis was tested in a rodent aortic transplantation model. METHODS: Donor descending aortas from August-Copenhagen-Irish rats were heterotopically transplanted into Lewis rat abdomens in end-to-end fashion. Animals were assigned to six groups as follows: AGI-1096 0 mg/kg per day (vehicle, n = 10), 10 mg/kg per day (n = 10), 20 mg/kg per day (n = 10), 40 mg/kg per day (n = 10), positive control (cyclosporine A 10 mg/kg per day by oral gavage, n = 10), and isograft negative control (Lewis-to-Lewis, n = 5). AGI-1096 was administrated subcutaneously to recipient animals three days before the surgery and for 90 days thereafter. On day 90, the paraffin-embedded allograft sections were stained with Elastin-van Gieson's stain, and the intima/media (I/M) ratio and luminal narrowing (1%LN) was assessed by digital morphometry. RESULTS: AGI-1096 demonstrated dose-dependent lowering of the I/M ratio and %LN when compared with vehicle controls. CONCLUSION: This is the first study to show that treatment of allograft recipients with AGI-1096 decreases the incidence of transplant arteriosclerosis. These data suggest that AGI-1096 may be a promising new therapeutic agent for use in clinical transplantation.

Animals↗
PubMed2004

Mycophenolate mofetil prevents transplant arteriosclerosis by direct inhibition of vascular smooth muscle cell proliferation.

UNLABELLED: BACKGROUND.: Transplant arteriosclerosis is one of the main features of chronic graft failure in organ transplantation. In this article, the authors investigate mechanisms of mycophenolate mofetil (MMF) on prevention of transplant arteriosclerosis in a rat aortic allograft model. METHODS: Orthotopic rat abdominal aortic transplantation was performed from Brown Norway (RT1) to Lewis (RT1) rats. The recipients were divided into three oral treatment groups: (1). vehicle; (2). MMF40 (40 mg/kg); and (3). MMF20 (20 mg/kg). The authors histologically and immunohistochemically evaluated neointima formation; infiltration of macrophages and T cells; and expression of endothelin (ET)-1, platelet-derived growth factor (PDGF)-B, PDGF receptor-beta (Rbeta), transforming growth factor (TGF) beta 1, and osteopontin (OPN). Using cultured rat vascular smooth muscle cells (VSMC), effects of mycophenolic acid (MPA) on ET-1-induced proliferation and ERK1/2 activation were also examined in vitro. RESULTS: In the vehicle group, marked neointima formation was observed, with massive macrophages and T-cell infiltration in neointima, media, and adventitia. Marked expression of ET-1, PDGF-B, PDGFR-beta, TGFbeta1, and OPN were also observed in neointima. In the MMF40 and MMF20 groups, neointima formation was halted, but macrophages and T cells were infiltrated in the adventitia and adhered to the endothelium. In the MMF40 group, medial infiltration by macrophages and T cells and intimal expression of ET-1, PDGF-B, PDGFR-beta, TGFbeta1, and OPN was inhibited compared with the vehicle and MMF20 groups. Furthermore, MPA inhibited ET-1-induced VSMC proliferation but failed to inhibit its ERK1/2 activation. CONCLUSIONS: MMF treatment might have preventive potential in transplant patients with chronic vasculopathy through inhibition of VSMC proliferation.

Animals↗
PubMed1998

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans.

BACKGROUND: Ketamine in sub-dissociative doses has been shown to have analgesic effects in various pain conditions, including neuropathic and phantom-limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood. METHODS: Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS). RESULTS: Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all the patients at the highest dose (0.45 mg/kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. These 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/kg ketamine doses than for morphine 10 mg. CONCLUSION: We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.

Aged↗
PubMed1994

Presence of polymorphonuclear granulocytes during the early stage of transplant arteriosclerosis after prolonged ischemia in the rat.

The presence and function of polymorphonuclear granulocytes has been investigated, in particular, in the microcirculation in many short-term models of ischaemia/reperfusion injury. The aim of this study was to examine the presence of granulocytes in the aorta in a recently established long-term model of transplant arteriosclerosis, based on prolonged cold graft ischaemia time in the rat. Aortic grafts of PVG donors were subjected to two different cold ischaemia times of 1 and 4 h (n = 5 in each group) before an orthotopic transplantation to syngeneic recipients. The grafts were explanted shortly after various times post-reperfusion (7.5 min 24 h) and examined with conventional staining, immunohistochemistry and transmission electron microscopy for the presence of granulocytes. The results showed the presence of these cells adherent to the endothelial layer or in the subendothelial layer in grafts with both ischaemia times and with a maximum seen 2 h after transplantation. The internal elastic lamina was interrupted at sites of granulocyte adherence. We concluded that the polymorphonuclear granulocyte may be involved in the ischaemia/reperfusion injury in this model, thus, contributing to the development of accelerated transplant arteriosclerosis.

Animals↗
PubMed2005

Longitudinal left ventricular myocardial dysfunction assessed by 2D colour tissue Doppler imaging in a dog with systemic hypertension and severe arteriosclerosis.

A 12-year-old sexually intact male Vendee Griffon Basset was presented for acute pulmonary oedema. Severe systemic systolic arterial hypertension (SAH) was diagnosed (290 mmHg). Despite blood and abdominal ultrasound tests, the underlying cause of the systemic hypertension could not be determined, and primary SAH was therefore suspected. Conventional echocardiography showed eccentric left ventricular hypertrophy with normal fractional shortening. Despite this apparent normal systolic function, 2D colour tissue Doppler imaging (TDI) identified a marked longitudinal systolic left ventricular myocardial alteration, whereas radial function was still preserved. Three months later, the dog underwent euthanasia because of an acute episode of distal aortic thromboembolism. Necropsy revealed severe aortic and iliac arteriosclerosis. SAH related to arteriosclerosis is a common finding in humans, but has not been previously described in dogs. Moreover, its consequence on longitudinal myocardial function using TDI has never been documented before in this species.

Animals↗
PubMed1991

Ultrastructural studies of rat arteriosclerosis induced by stimulation of the immune system with ovalbumin.

Intimal thickening in the aorta and carotid artery of rats was induced by repeated intraperitoneal injections of ovalbumin, 2.5 mg/kg BW, given weekly 5 times after initial subcutaneous sensitization, and/or feeding with a cholesterol-rich diet. The intimal thickening was apparent in immune-challenged rats fed with either a cholesterol-rich or a basal diet (p less than 0.01), whereas it was mild in non-immunized rats fed a cholesterol-rich diet. The ultrastructural changes in the thickened intima were characterized by leukocytic (mainly monocytic) adhesion and migration, and minor endothelial cell damage. Morphometric evaluation of leukocyte adhesion to the intima of the thoracic aorta revealed that the immunized rats fed either a cholesterol-rich or a basal diet showed greater leukocytic adhesion (p less than 0.01 and p less than 0.001, respectively) than that in non-immunized rats fed a cholesterol-rich diet, which in turn also showed an increased degree of leukocyte adhesion (p less than 0.05) than control rats. This immunological approach to the arteriosclerotic process could explain the earlier and more severe arteriosclerosis found in patients with immunological disorders, and the development of arteriosclerosis in the absence of hypercholesterolemia, hypertension and other risk factors.

Animals↗
PubMed1990

Adrenaline and noradrenaline as possible chemical mediators in the pathogenesis of arteriosclerosis.

We studied the relationships between adrenaline and noradrenaline and factors associated with arteriosclerosis to determine whether catecholamines contribute to the atherogenetic process. We investigated the effects of adrenaline and noradrenaline on cultures of vessel wall cells from rats and analyzed plasma catecholamine levels in humans exposed to atherogenic risk factors, undergoing hemodialysis treatment or following myocardial infarction or stroke. I. Cultured endothelial and smooth muscle cells from vessel walls exhibited enhanced proliferation when exposed to adrenaline or noradrenaline. This indicates that catecholamines trigger the activation of vascular wall cells in vitro. Such activation, the unspecific mesenchymal reaction, is the predominant characteristic change in early atherogenesis. II. In individuals subjected to the atherogenic risk factors smoking, essential hypertension and mental stress, plasma adrenaline concentrations were statistically significantly elevated. Mental stress also caused significantly elevated plasma noradrenaline levels. Plasma noradrenaline concentrations were also elevated in smoking and hypertensive individuals when compared with certain controls, but the differences failed to be statistically significant. III. In dialysis patients, plasma adrenaline and noradrenaline concentrations showed a positive correlation with the activity of the sclerotic process; i.e., plasma catecholamine concentrations increased with the severity of the disease. IV. Patients with persisting arteriosclerotic vascular disease, i.e., patients who had had a myocardial infarction or stroke, had significantly elevated plasma adrenaline and/or noradrenaline levels as late as one year after the event. The results of our investigations suggest that adrenaline and noradrenaline may act as chemical mediators during atherogenesis in man, thus contributing to the development and subsequent complications of arteriosclerosis.

Arteriosclerosis↗
PubMed1992

Arteriosclerosis. Impairment of cellular interactions in the arterial wall.

Our understanding of the cellular interactions in the arterial wall has increased considerably during the last 15 years. It has become clear that arteriosclerosis is a multifaceted disease, in which the accumulation of monocyte-derived macrophages, smooth muscle cells, T-lymphocytes, and lipid deposits contributes to the progressive thickening of the arterial intima. Many different types of stress, including cholesterol-rich lipoproteins, smoking, hypertension, hyperfibrinogenemia, endothelial damage, and inflammatory activation, contribute to this derailed "repair" response in the arterial intima. They are recognized as risk factors for cardiovascular disease. As a consequence of the progressive thickening of the arterial intima, the arterial lumen narrows, the barrier, vasoregulatory, and anticoagulant properties of the endothelium become impaired, and the arterial wall becomes prone to rupture and thrombosis. The advanced lesions can cause serious complications: myocardial infarction, stroke, claudication, and angina pectoris. As the extent of arteriosclerosis increases with age--a process that is accelerated by risk factors--it has a particular impact on the mortality and the quality of life of elderly people.

Aged↗
PubMed1985

The ophthalmological findings in autosomal recessive severe juvenile arteriosclerosis.

Severe juvenile arteriosclerosis (JAS) is a rare, fatal disease with probably autosomal recessive inheritance. Precocious arterial murmurs and calcification of aorta and major arteries are associated with anaemia, growth retardation, prolonged systolic hypertension, gradual renal failure, gastrointestinal perforations, and early death. The ophthalmological findings in 5 boys and 1 girl between 7 and 17 years of age were retinal vascular tortuosity of main vessels, pre-capillary arterioles and post-capillary venules, sausage-like bulging of central main arterioles and microaneurysms of arterioles of the central fundus. Narrowing and local constriction was a typical feature of peripheral arterioles. The combination of findings documented by fluorescein angiography in 4 children was typical for severe juvenile arteriosclerosis.

Adolescent↗
PubMed2006

Synergistic suppression of rat neointimal hyperplasia by rapamycin and imatinib mesylate: implications for the prevention of accelerated arteriosclerosis.

BACKGROUND: Accelerated arteriosclerosis remains a major limitation to therapeutic interventions such as angioplasty, stent deployment, and solid organ transplantation. Rapamycin, a powerful new immunosuppressant set to replace calcineurin inhibitors in the transplant setting, and imatinib mesylate, a receptor tyrosine kinase inhibitor, are both angioprotective. Here, we explored the pharmacological and therapeutic interactions of these two agents in a rat model of neointimal hyperplasia. METHODS: Wistar rats, subjected to balloon catheter-induced aortic injury, received daily drug treatment until postoperative day 14 and were subsequently sacrificed or followed up to day 40 without further treatment. Development of neointimal lesions was assessed histologically and immunohistochemically. Steady-state rapamycin levels in whole blood were determined by HPLC-UV. RESULTS: Rapamycin and imatinib, administered individually or in combination, produced no signs of overt toxicity. Continuous postoperative therapy with either rapamycin (0.5-1.5 mg/kg/day) or imatinib (2- 50 mg/kg/day) dose-dependently suppressed neointimal hyperplasia on day 14. Combined treatment (0.5 or 1 + 10 mg/kg/day, respectively) showed a trend towards synergistic action on day 14. Withdrawal of medication on day 14 nullified the early therapeutic effect of either agent by day 40. In contrast, early combination therapy (1 + 10 mg/kg/day) achieved long-term suppression of neointimal hyperplasia by approximately 81%. Notably, coadministration of imatinib appeared to reduce exposure to rapamycin, although this finding did not reach statistical significance. CONCLUSIONS: Short-term combination therapy with rapamycin and imatinib is well tolerated and produces synergistic, sustained suppression of neointimal hyperplasia in rats. Subject to clinical evaluation, this new drug regimen may afford definitive prophylaxis against accelerated arteriosclerosis.

Angioplasty, Balloon↗
PubMed1992

Role of adrenal androgens in the development of arteriosclerosis as judged by pulse wave velocity and calcification of the aorta.

To evaluate the role of adrenal androgens in the development of arteriosclerosis, serum dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), aortic calcification and pulse wave velocity (PWV) were measured in 69 males and 119 females without overt cardiovascular disease. The steroids decreased with age in both sexes, and the reduction was significantly steeper in younger (< or = 40 years) than in older (> 40 years) subjects only in females. When adjusted for age, the steroids were significantly lower in subjects with aortic calcification than in those without it, and the PWV was significantly slower in the latter. Adrenal androgens appear to retard the development and/or progression of arteriosclerosis.

Adolescent↗
PubMed1986

Quantitative detection of cerebral arteriosclerosis by means of the Doppler ultrasonic technique.

A correlation between the continuity of the cerebral blood flow pattern and the cerebral vascular resistance (namely, cerebral arteriosclerosis) was investigated by the Doppler ultrasonic technique. The following facts were observed. Examination of the brachial blood flow pattern in circulatory stress, i.e., hand-grasping, brachial-binding, cold- and warm-stimulating tests revealed that the more the peripheral vascular resistance was increased, the more was the discontinuity of brachial blood flow pattern increased. Investigation of the continuity of the cerebral blood flow pattern (internal carotid artery) in 18 young healthy persons and 46 elderly patients with cerebral vascular diseases revealed a continuous pattern in all of the young persons, while the discontinuous pattern was frequently observed in the elderly patients. These findings suggest that the cerebral vascular resistance is more increased in the elderly patients than in the young persons. The cerebral blood flow pattern was classified into the following three types according to the continuity of the cerebral blood flow pattern: continuous, intermediate and discontinuous type, and the relation to the Continuous Index (CI), which was devised as an objective parameter of the continuity, was examined. The following CI figures were obtained: 110-200% in the young persons; in the elderly patients: continuous type, 120-185%; intermediate type, 85-135%; discontinuous type, 50-85%. From the above findings it is postulated that the Doppler ultrasonic technique is useful for the quantitative detection of cerebral arteriosclerosis, i.e., anticipation of cerebral vascular accidents, and for the discrimination between arteriosclerotic dementia and Alzheimer's disease.

Age Factors↗
PubMed2006

Critical role of inducible costimulator signaling in the development of arteriosclerosis.

OBJECTIVE: Proliferation and migration of smooth muscle cells (SMCs) and migration and accumulation of monocytes and T cells are landmark events in the development of arteriosclerosis. SMC proliferation in the intima induces interruption of blood flow and results in ischemia and graft rejection. Inducible costimulator (ICOS) is a major costimulator of T cell activation. However, the effect of costimulatory molecules on the formation of neointimal hyperplasia has not been fully elucidated. We examined the role of the ICOS pathway in SMC proliferation. METHODS AND RESULTS: ICOS ligand (ICOSL) was detected in SMCs stimulated by interleukin (IL)-1beta, and coculture of stimulated SMCs and activated T cells induced SMC proliferation. Inhibition of the ICOS pathway resulted in inhibition of SMC proliferation. In models of transplantation and vascular injury, ICOSL was induced in SMCs in the neointima. Expression of IL-1beta, a key inducer of ICOSL expression, was significantly reduced in mice treated with anti-ICOS antibody or soluble form of ICOS (ICOSIg) and in ICOS-deficient mice. Inhibition of the ICOS pathway significantly suppressed neointimal thickening. CONCLUSIONS: These results indicate that ICOS on activated T cells contributes to neointimal formation through the regulation of SMC proliferation. These findings provide insights into new therapeutic strategies for arteriosclerosis.

Animals↗
PubMed1994

Platelet calcium homeostasis is abnormal in patients with severe arteriosclerosis.

To evaluate platelet calcium homeostasis in a typical thrombosis-prone clinical condition, 14 patients with severe arteriosclerosis and 11 healthy control subjects were studied. Platelet intracellular free calcium concentration ([Ca2+]i) was evaluated by means of the fluorescent probe fura 2 under resting conditions and after challenge with 0.05, 0.1, and 0.5 U/mL thrombin (final concentrations). Three different concentrations of extracellular ionized calcium ([Ca2+]e) were used: 1 mmol/L, 1 mumol/L, and < 1 nmol/L. Resting platelet [Ca2+]i was significantly higher (P < .001) in patients than in control subjects. After addition of 0.05 U/mL thrombin, the relative increase of [Ca2+]i was lower in patients than in control subjects in each of the three [Ca2+]e conditions (P = .05 at 1 mmol/L, P = .02 at 1 mumol/L, and P = .04 at < 1 nmol/L). After addition of 0.1 U/mL thrombin, the relative increase of [Ca2+]i was lower in patients than in control subjects under two [Ca2+]e conditions, 1 mumol/L and < 1 nmol/L (P = .04 and P = .03 respectively). With 0.5 U/mL thrombin, a trend toward lower values in patients than in control subjects was observed, reaching statistical significance (P = .03) only at < 1 nmol/L [Ca2+]e. These results suggest that calcium homeostasis is abnormal in platelets from patients with severe arteriosclerosis and probably reflects a chronic activation.

Adult↗
PubMed1996

Ischemia-induced transplant arteriosclerosis in the rat. Induction of peptide growth factor expression.

Peptide growth factors have been reported to contribute to the atherogenic process, and they are known to mediate signals for vascular remodeling. Using syngeneic and allogeneic rat aorta transplant models, we analyzed the impact of cold ischemia time up to 24 hours and reperfusion injury on development of transplant arteriosclerosis during the first 2 months after transplantation. The expression of the transforming growth factor-beta (TGF-beta) family as well as the platelet-derived growth factor (PDGF) and its receptors was studied by use of immunohistochemistry, followed by semiquantitative evaluation and multivariate analysis. In the syngeneically transplanted aortas, the expression of TGF-beta 1, PDGF, and the two PDGF receptors in the neointima increased significantly with the extent of cold ischemia time. Furthermore, there was a significant induction of the latent TGF-beta binding protein in the neointima as well as TGF-beta 2 in the media, both correlating with the observation time after transplantation. In the allogeneic grafts, all examined proteins were already induced strongly 2 weeks after transplantation, even at the shortest ischemic period studied (1 hour). However, no positive correlation between growth factor expression and cold ischemia or observation time could be found. Double immunohistochemistry revealed that macrophages express PDGF and its receptors as well as TGF-beta 1. Smooth muscle cells express both types of PDGF receptors, and a few T cells express TGF-beta 1 as well as PDGF receptors. In summary, TGF-beta and PDGF are induced by allogeneic as well as ischemic stimuli in transplanted aortas, suggesting a role in the pathogenesis of transplant arteriosclerosis and representing a potential target for therapeutic intervention.

Animals↗
PubMedDate not supplied

Morphometry of air-drying-induced arteriosclerosis in rat carotid artery. Effect of air-flow rate.

Arteriosclerosis in the Wistar rat carotid artery was induced by air drying of the endothelium, a procedure that caused media necrosis. We describe a number of technical modifications that facilitate the procedure and minimize damage to the vessel wall (i.e., media necrosis). A morphometric study of vessel wall changes induced by endothelial denudation at various air-flow rates showed that necrosis of the inner medial layer and lesion size and position were constant at all flow rates used (greater than or equal to 28 ml/min). The extent of necrosis of the outer medial layers, the endothelial repair, and the shape of the lesions varied with the air-flow rate used. Since at an air-flow rate of 28 ml/min medial necrosis was minimal and myointimal lesion development was as extensive as at higher flow rates, we consider this air-flow rate to be optimal for this model of experimental arteriosclerosis. We hypothesize that the shape of the myointimal lesion is determined by the timespan of endothelial denudation and by the availability of smooth muscle cells in necrotic and normal media. Furthermore, the proliferation of the smooth muscle cells and their migration into the intima is probably dominant over the repopulation of the media by these cells.

Air Movements↗