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PubMed2001

Nerve growth factor levels and mast cell distribution in human coronary atherosclerosis.

Nerve growth factor (NGF), in addition to its neurotrophic function, acts on a variety of non-neuronal cells including immune cells and vascular smooth muscle cells. The aim of the present study was to determine the NGF levels and the distribution of NGF and low-affinity NGF receptor (p75NGFR) and mast cells (MC) in human atherosclerotic coronary arteries. Specimens of human coronary arteries obtained from autopsy cases (n=12, subjects with atherosclerotic lesions; n=9, subjects without atherosclerotic lesions/controls) were used. The present study showed that in the atherosclerosis-lesioned arteries, the amount of NGF decreased, whereas the expression of p75NGFR immunoreactivity and the number, both of MC and vasa vasorum, particularly in the adventitia, significantly increased, compared with the control arteries. Cumulatively, our findings help to set the neurotrophic theory and its currently extended neuroimmune framework into the context of pathobiology of atherosclerosis, suggesting that altered presence of NGF, p75NGFR, and MC may play a role in neuroimmune mechanisms of human coronary atherosclerosis.

Adult↗
PubMed1991

Histology and morphometry of Strongylus vulgaris-mediated equine mesenteric arteritis.

Histological and morphometric evaluation of equine cranial mesenteric arteries was performed on 239 and 89 arteries, respectively. Histological examination revealed that thrombosis and the severity of inflammation varied on a seasonal basis and were directly associated with larval presence. Intimal and adventitial fibrosis were generally of greater severity than medial fibrosis. Fibrosis of the vasa vasorum was less frequent than fibrosis of the artery itself. Morphometry revealed a significant increase in intimal, adventitial and, to a lesser extent, medial area in affected as compared with normal arteries. This change was due to the accumulation of collagen and was considered to result in decreased arterial elasticity. The luminal area varied widely among affected arteries.

Animals↗
PubMed2003

Impact of aging on the body's vascular system.

In this review, the effect of aging on the body's vascular system is considered in terms of potential mechanisms involved in target organ damage. First, the effects of aging on body fluid compartments, including changes that occur in subdivisions of the interstitial space (quite heterogeneous among organs), are described, with particular reference to the macromolecular composition of the fluid compartments. Second, the structure and function of different segments of the vascular system during aging are examined, with emphasis on: (1) large arterial conduits responsible for isolated systolic hypertension; (2) arteries most responsible for peripheral resistance (the "resistance arteries"); (3) microcirculation networks, including the vasa vasorum; and (4) large collecting veins that can have such an important effect on the cardiac output. Third, a detailed discussion is provided of the heterogeneous macromolecular composition of interstitial fluid compartments that are involved in the critical traffic of vital substrates, including pharmacologic agents, in transit from the systemic circulation to the various organs. The strategic position of interstitial fluid compartments, situated as they are between microcirculation networks and vital organs, is considered to be critically involved in the morbidity and mortality caused by the vascular diseases afflicting elderly persons. Finally, with respect to "physiological" and/or "morbid" aging, a re-examination is undertaken of the target organ damage observed in elderly individuals who suffer from isolated systolic hypertension, type II diabetes mellitus, peripheral vascular disease, chronic heart failure, and renal failure. Potentially new and noninvasive approaches available to clinicians for early detection of large artery rigidity are considered, along with the possible benefits of nonpharmacologic and/or pharmacologic interventions.

Aging↗
PubMed1997

Elastin degradation products induce adventitial angiogenesis in the Anidjar/Dobrin rat aneurysm model.

BACKGROUND: Infusion of the abdominal aorta with pancreatic elastase induces aneurysms in a rat model (Anidjar/Dobrin). Because elastolysis liberates elastin degradation products (EDPs), the present experiment was carried out to test the hypothesis that an EDP alone could induce features of aneurysm disease. METHODS: The EDP val/gly/val/ala/pro/gly (VGVAPG), elastase, or saline solution was infused into infrarenal aorta (n = 4/group). After 1 week aortic diameters were measured, and the tissues were prepared for histologic examination. Adventitial capillaries (vessels per high-power field) were counted over a standardized preparation of aorta. Wall thickness was measured by means of computer-aided planimetry. RESULTS: There was an increase of greater than 100-fold in mean vessels per high-power field in aortas receiving VGVAPG or elastase versus saline controls (4.10 +/- 0.68 SEM or 4.48 +/- 0.49 SEM versus 0.03 +/- 0.03 SEM, respectively, p < 0.05). The VGVAPG-perfused group had a 26% +/- 4% SEM increase in diameter from baseline that was statistically significant (p < 0.01), but the aortas did not reach aneurysmal dimensions. CONCLUSIONS: Although no aneurysms occurred at 1 week after the infusion of EDP, the results demonstrate that the EDP VGVAPG can induce a characteristic feature of aneurysm disease. The model permits study of the earliest stages of experimental aneurysm formation and raises interesting questions regarding the role of the vasa vasorum in this pathologic process.

Animals↗
PubMed1986

In situ saphenous vein bypass for occlusive disease in the lower extremity.

In situ saphenous vein bypass, using the new valve incision techniques, has shown great promise in the early clinical trials to date. This procedure allows disruption of the venous valves without removal of the vein from its bed, thus allowing preservation of the vasa vasorum and maintenance of the endothelial integrity of the veins. This has allowed an overall improvement in the patency rates of the lower extremity bypasses, particularly in the bypasses to the infrapopliteal position. Also, and perhaps most important, it has permitted the use of smaller veins, with a minimum diameter of 2 mm. This greatly increases the number of patients who can benefit from such a vein bypass since reversed vein bypasses previously have required veins to have a minimum diameter of 3.5 to 4 mm. Long-term follow-up of in situ bypasses is not yet available. However, if the encouraging preliminary results of these bypasses are substantiated on long-term follow-up, in situ saphenous vein bypass may well become recognized as the procedure of choice for lower extremity bypass.

Amputation, Surgical↗
PubMed1983

The morphology of ascending aortic aneurysms.

To determine the frequency of morphologic abnormalities of the aorta, especially of the media, in patients with aneurysms of the ascending aorta, tissue specimens from surgically resected ascending aortic aneurysms of 339 patients were studied. Included were 232 men and 107 women; 53 (29 men, 23 women) had clinical signs of Marfan's disease. Features evaluated and graded included fragmentation of elastic fibers, cystic medial change, medial fibrosis, medial necrosis, atherosclerosis, periaortic fibrosis, and thickening of the vasa vasorum. Both elastic fragmentation and cystic medial change were present in a high percentage of patients. Cystic medial change was inversely correlated with increasing age of patients, especially in the group of patients without clinical evidence of Marfan's syndrome. Marked changes of these types in many younger patients without Marfan's syndrome could reflect a "tissue insufficiency" in early life that causes the aortic wall to weaken and dilate. Medial necrosis, fibrosis, and atherosclerosis were directly correlated with age. Hemodynamic events are considered to initiate injury and repair within the aortic wall. Dissection was more frequently seen with medial abnormalities than with atherosclerosis.

Adult↗
PubMed1999

Mast cells are augmented in deep vein thrombosis and express a profibrinolytic phenotype.

A number of recent data suggest that mast cells (MC) and their products are involved in the pathophysiology of thrombosis. In the current study, we have evaluated the number, distribution, and phenotype of MC in patients with deep vein thrombosis of the lower limb (DVT) (n = 15). Contralateral nonthrombosed limb veins served as control (CO). MC were examined by Giemsa staining and by immunohistochemistry using antibodies against tryptase, chymase, tissue-type plasminogen activator (tPA), urokinase (uPA), urokinase receptor (uPAR), and plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the number of tryptase-positive MC in DVT compared with CO (DVT: 9.1+/-1.0 v CO: 4.7+/-0.6 MC/mm2, P < .05). Most of these MC appeared to accumulate in the adventitia of the thrombosed veins, in vicinity of the vasa vasorum. In both DVT and CO, MC reacted with monoclonal antibodies to c-kit, tryptase, and chymase. MC also stained positive for tPA and urokinase receptor, but did not express detectable PAI-1 or PAI-2. As compared with CO, a decreased proportion of MC in DVT was found to stain positive for chymase and tPA. Together, our results show that MC increase in number in DVT and express a profibrinolytic phenotype. We hypothesize that MC and MC-derived profibrinolytic molecules play a role in the pathophysiology of DVT.

Aged↗
PubMed1997

Age-related changes of the noradrenergic innervation of rat tracheo-bronchial tree and pulmonary vasculature.

Age-related changes of the noradrenergic innervation of the tracheo-bronchial tree and of pulmonary vasculature were investigated in male Wistar rats of 3 months (young), 12 months (adult) and 24 months (old/aged), using catecholamine histofluorescence techniques associated with image analysis and by high pressure liquid chromagraphy with electrochemical detection. In young rats, blue-green fluorescent nerve fibres supply tracheo-bronchial smooth muscle and tracheal and bronchial glands, which are innervated by a delicate network of nerve fibres rich in varicosities. Pulmonary artery and vein are sparsely innervated. They are supplied with nerve fibres distributed in the vasa vasorum or the adventitia and the outer tunica media. The higher noradrenaline concentrations were found in the trachea and extraparenchymal bronchi, followed by pulmonary vein and pulmonary artery. The density and pattern of noradrenergic innervation of the tracheo-bronchial tree, or of the pulmonary vasculature, were similar in young and adult rats. In aged rats, a loss of noradrenergic innervation involving primarily the supply to the smooth muscle of the tracheo-bronchial tree was observed. Histofluorescence techniques demonstrated a higher sensitivity than noradrenaline assay in detecting changes of the sympathetic innervation of the tracheo-bronchial tree and of the pulmonary vasculature. The possible significance of reduced noradrenergic innervation of the tracheo-bronchial tree in aged rats is discussed.

Adrenergic alpha-Agonists↗
PubMed1993

Intermediate filaments and ATPase activity in the vascular wall of vertebrates.

The vascular wall of aorta and vena cava was examined for adenosine triphosphatase (ATPase) activity and cytoskeletal intermediate filaments (IF) in different representatives of vertebrates. Enzyme activity was studied by the modified method of Padykula and Herman. A streptavididin-biotin immunohistochemical method was applied to reveal desmin (D) and vimentin (V) IF. Endothelial cells of all vessels were V-positive and D-negative and exhibit high ATPase activity. Vascular smooth muscle cells (SMC) in lower vertebrates (pisces and amphibia) were also V-positive and D-negative, but showed low ATPase activity. SMC were D-positive and V-negative and possessed high enzyme activity in aves and mammals, similar to that of the endothelium. In cow vascular wall D-reactivity and high ATPase activity were mostly expressed in bundles of mosaically arranged thick SMC fibres of the outer aortic media as well as in the longitudinal fibres in the inferior vena cava. In higher vertebrates SMC of vasa vasorum were both V- and D-positive and showed high enzyme activity. The results demonstrate that D-immunoreactivity is mostly expressed in SMC of layers of high functional activity, which correlates with the intense ATPase reaction in these cells.

Adenosine Triphosphatases↗
PubMed1980

The cholinergic innervation of the aorta.

The cholinergic innervation of the aorta has been studied in some mammalian species. Cholinergic nerve fibers (CNF) are organized in the aorta of the rabbit, kid, lamb, and guinea pig in 2 plexuses. The plexuses of CNF consist of a superficial plexus localized in the adventitial layer and a deep one localized in the adventitial-medial transitional zone. Some CNF reach the outer layers of the media. In the aorta of the dog, mouse and rat CNF are organized in a single plexus localized in the adventitial layer. This nerve plexus is formed of CNF that for the most part are distributed to the vasa vasorum. The chemical sympathectomy don't alters the pattern of the cholinergic innervation of the aorta, indicating that stained CNF are parasympathetic in nature. The meaning of a cholinergic innervation of the aortic wall is discussed.

Animals↗
PubMed2000

Intracranial aneurysms and arterial hypertension: a review and hypothesis.

BACKGROUND: Intracranial aneurysms and systemic arterial hypertension coexist in a high percentage of patients. The relationship between intracranial aneurysms and hypertension is poorly defined. METHODS: Therefore, we reviewed the role of hypertension in the pathogenesis of saccular aneurysms as previously reported in clinical, experimental, and autopsy studies. RESULTS: Among 24 relevant clinical and/or autopsy studies, the mean incidence of pre-existing hypertension was 43.5% in aneurysm patients compared to 24.4% in the normal population. Although definitive evidence is lacking, data from multiple types of investigations indicate that systemic arterial hypertension creates a greater risk for the development of intracranial aneurysms than previously believed. The underlying pathophysiological mechanism(s) are also poorly defined. CONCLUSIONS: We propose a unifying hypothesis: Endothelial injury, occlusion of the vasa vasorum, and disruption of the synthesis of collagen and elastin are likely the most important factors in initiating the development of aneurysms. Chronic hypertension potentially affects all of these factors. Consequently, chronic hypertension may cause intimal thickening, necrosis of the tunica media, changes in the compositional matrix, and degeneration of the internal elastic lamina to develop in the arterial wall. These structural changes could cause a focal weakening in the arterial wall with resultant bulging. This theory accounts for the high incidence of intracranial aneurysms in the absence of any known associated hereditary or connective-tissue disease. Nor does it exclude the possibility of other etiological factors. From the perspective of prevention, however, it offers clear opportunities for prophylaxis.

Adolescent↗
PubMed1999

Invasion of the internal carotid artery by cavernous sinus meningiomas.

BACKGROUND: Meningiomas are the most common tumor involving the cavernous sinus. Although these tumors have been known to invade adjacent structures such as bone, soft tissue, and brain, invasion of the internal carotid artery (ICA) by meningiomas has only been recognized recently. The authors evaluate the extent of carotid wall involvement in nine patients with cavernous sinus meningiomas encasing the ICA who underwent en bloc resection of the cavernous sinus. METHODS: The en bloc tumor-ICA specimens were fixed in formalin, embedded in paraffin, and sectioned on a rotary microtome. Hematoxylin and eosin, EVG, and HVG stains were performed and evaluated by light microscopy. RESULTS: There were four males and five females with a mean age of 47 years. Eight patients had not undergone previous surgery, whereas one patient had been operated on before. In this latter case, however, the cavernous sinus was not entered during the first operation. In all patients, stenosis of the ICA was confirmed by preoperative angiography and/or magnetic resonance imaging (MRI). In seven cases, the tumors were excised en bloc along with the stenotic ICA segment. A petrous-to-supraclinoid ICA bypass was performed in these seven patients. In two cases, the tumor was excised with the stenotic artery, but no bypass was performed. The final pathological diagnosis was meningothelial meningioma. In all cases tumor cells were found in the adventitia of the cavernous carotid with stenosis of the arterial lumen. Compression and/or obliteration of the vasa vasorum within the adventia was noted in all specimens. In four cases, the tumor was found to have invaded the external elastic lamina. In two instances the external elastic lamina was disrupted and the tumor focally extended into the media. CONCLUSIONS: These findings suggest that in the case of cavernous sinus meningiomas with encasement and stenosis of the intracavernous ICA, invasion of the vessel wall has occurred. The effect of these findings on the management of cavernous sinus meningiomas and the involved ICA is discussed.

Adult↗
PubMed1999

Up regulation of AT4 receptor levels in carotid arteries following balloon injury.

Angiotensin IV, (V-Y-I-H-P-F), binds to AT4 receptors in blood vessels to induce vasodilatation and proliferation of cultured bovine endothelial cells. This latter effect may be important not only in developing tissues but also in injured vessels undergoing remodelling. In the present study, using normal rabbit carotid arteries, we detected AT4 receptors in vascular smooth muscle cells and in the vasa vasorum of the adventitia. Very low receptor levels were observed in the endothelial cells. In keeping with the described binding specificity of AT4 receptors, unlabelled angiotensin IV competed for [125I]angiotensin IV binding in the arteries, with an IC50 of 1.4 nM, whereas angiotensin II and angiotensin III were weaker competitors. Within the first week following endothelial denudation of the carotid artery by balloon catheter, AT4 receptor binding in the media increased to approximately 150% of control tissue. AT4 receptor binding further increased in the media, large neointima and re-endothelialized cell layer to 223% at 20 weeks after injury. In view of the known trophic effects of angiotensin IV, the elevated expression of AT4 receptors, in both the neointima and media of arteries, following balloon injury to the endothelium, suggests a role for the peptide in the adaptive response and remodelling of the vascular wall following damage.

Angioplasty, Balloon, Coronary↗
PubMed2000

Aortitis syndrome associated with positive perinuclear antineutrophil cytoplasmic antibody: report of three cases.

We recently experienced three cases of aortitis syndrome that were associated with perinuclear antineutrophil cytoplasmic antibody (ANCA). In the three cases, roentgenographic examination revealed the typical appearance of stenosis or occlusive subclavian arteries. In addition, two cases showed a thickened thoracic aorta wall and the remaining case had irregular stenosis of both common iliac arteries. All three cases had persistently increased ESR and CRP over the years. These findings suggested the diagnosis of aortitis syndrome. ANCA tests were performed because of rapidly progressive glomerulonephritis symptoms in two patients and marked excretion of beta(2)-microglobulin in urine in one patient. The test showed P-ANCA in all three patients, with two patients identified as anti-MPO antibody and the third patient as non-MPO antibody. The implication of ANCA in the pathogenesis of aortitis syndrome is presumed to be: ANCA, which plays an important role in the pathogenesis of small vessel vasculitis, induces vasculitis of the vasa vasorum in the aorta or main branches (or both) and this pathologic process results in the pathogenesis of aortitis syndrome.

Aged↗
PubMed2000

Pathogenic principles in giant cell arteritis.

In giant cell arteritis, an immune insult in the vascular wall initiates a reaction in the artery that leads to structural changes, intimal hyperplasia, and luminal occlusion. The mechanisms triggering the immune stimulation are unknown; however, the process is strictly dependent on T cells that are found in the vicinity of the vasa vasorum in the adventitia and that produce interferon-gamma. The major effector cells in the artery are macrophages and giant cells that are ultimately under T-cell control but assume different functions depending on their location in the arterial wall. The response of the artery to the injury is maladaptive and includes mobilization and proliferation of smooth muscle cells in conjunction with matrix production and neoangionesis, resulting in the formation of a lumen-obstructive neointima. Heterogeneity in the immune insult and the resulting arterial response patterns correlate with variations in clinical disease.

Aldehyde Reductase↗
PubMed1996

Angiographic findings in Buerger disease.

To clarify the angiographic findings in patients with Buerger disease and to elucidate the relationship between the angiographic findings and the clinical prognosis, 144 angiographic images of the lower extremities of 119 patients with Buerger disease have been studied. The present study has included patient data in our previous report. Results of this study revealed that in lower extremities showing a femoropopliteal arterial occlusion (n = 57), the frequency of gangrene was significantly lower statistically in limbs in which the main arteries of the lower leg and foot were well visualized (2 (12%) of 17 limbs) than in limbs in which the main arteries did not visualize (25 (63%) of 40 limbs) (P < 0.001). Further, in lower extremities showing a crural arterial occlusion (n = 59), the incidence of pedal gangrene increased as the extent of pedal arterial occlusion increased, though this rise was not statistically significant. Also, the collateral vessels had a 'corkscrew' appearance in 39 (27%) of 144 limbs affected by Buerger disease, whereas this appearance was seen in only 2 (3%) of 63 limbs of patients with arteriosclerosis obliterans (P < 0.001). Another finding of this study is that corkscrew-shaped vessels that extend from the sites of the arterial occlusion to the periphery of the feet without opacification of the main pedal arteries indicate a poor prognosis. Based on the above findings, we thus believe that the appearance of corkscrew-shaped vessels is the most characteristic feature of Buerger disease and that each represents a dilated vasa vasorum of the occluded main arteries.

Adult↗
PubMedDate not supplied

[Arterial manifestations of Behçet's disease. 12 cases].

Out of 196 patients with Behçet's disease, 12 (10 men and 2 women, mean age 34 +/- 7 years) had non-coronary arterial lesions. Behçet's disease was complete in 4 patients. The arterial lesions had appeared 8.6 +/- 8 years on average (20 years at most) after the first sign of the disease. Three patients showed evidence of stenosis or occlusion involving one or several arteries. Eight patients had both stenotic and aneurysmal lesions. One patient had an arteriovenous fistula. Another developed a false aneurysm at the site of introduction of a femoral catheter. Yet another patient developed an anastomotic aneurysm one year after implantation of an abdominal aortic graft. In 2 cases histology showed fragmentation of the media associated with vasculitis of the vasa vasorum. Two patients with pulmonary aneurysm died of massive haemoptysis. In 2 patients combined corticosteroid and cyclophosphamide therapy failed to prevent the development of aneurysmal lesions. Phlebitis was associated with arterial involvement in 7 patients. Comparison between patients with or without arterial lesions showed no significant difference in time of onset of Behçet's disease, sex, main clinical features and presence of HLA B5. Aneurysmal lesions respond poorly to medical treatment, and surgery is mandatory. Since recurrence at the site of anastomosis is possible, prolonged monitoring is required.

Adult↗
PubMed1997

Histologic correlates of angiographic chronic total coronary artery occlusions: influence of occlusion duration on neovascular channel patterns and intimal plaque composition.

OBJECTIVES: Age-related changes in histologic composition and neovascular channel (NC) pattern of angiographic chronic total coronary artery occlusions (CTOs) were studied to define histologic correlates of age-related revascularization profiles and neovascular channel formation. BACKGROUND: Revascularization of CTOs is frequently characterized by inability to cross or dilate the lesion and a high incidence of reocclusion or restenosis but low periprocedural ischemic complication rates. Little is known about the histopathologic basis of these observations. METHODS: Ninety-six angiographic CTOs from autopsy studies in 61 patients who had undergone coronary angiography within 3 months of death were studied. Abrupt plaque rupture was excluded. Occlusion segments were analyzed for 1) histologic composition as a function of lesion age; and 2) NC pattern as a function of lesion age and intimal plaque (IP) composition. RESULTS: Cholesterol and foam cell-laden IP was more frequent in younger lesions (p = 0.0007), whereas fibrocalcific IP increased with CTO age (p = 0.008). IP NCs arose directly from adventitial vasa vasorum and were anatomically and quantitatively related in terms of number and size (p = 0.0001) to the extent of IP cellular inflammation. IP cellular inflammation exceeded that found in the adventitia (p < 0.001) or media (p = 0.0001) across all CTO ages. In CTOs < 1 year old, the adventitia was associated with a larger number and size of NCs relative to the IP (p = 0.0006 and p = 0.009), media (p = 0.0001 and p = 0.002) and recanalized lumen (p = 0.0001 and p = 0.001). In CTOs >1 year old, the adventitia and IP NC numbers were similar and exceeded NC numbers found in the media (p = 0.0001) and recanalized lumen (p = 0.0001 and p = 0.003). CONCLUSIONS: Angiographic CTO frequently corresponds to less than complete occlusion by histologic criteria. Age-related changes in IP composition from cholesterol laden to fibrocalcific may explain the adverse revascularization profile of older CTOs. IP NC growth derived from the adventitia increases with age and is strongly associated with IP cellular inflammation. IP NC formation may protect against the flow-limiting effects of IP growth.

Adult↗