[Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]. / Actividad proliferativa y alteraciones cromosómicas de las células musculares lisas en la ateroesclerosis.

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Actividad proliferativa y alteraciones cromosómicas de las células musculares lisas en la ateroesclerosis. / [Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis]

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Hyperplasia of the aorticopulmonary paraganglia: a new insight into the pathogenesis of sudden infant death syndrome?

In this study, the Authors search for morphologic alterations in the aorticopulmonary paraganglia (APP) of sudden infant death syndrome (SIDS) victims when compared with age-matched controls. Morphometric studies on serial sections of the APP were performed with an image analyzer in combination with a standard microscope attached to a video camera. APP hyperplasia, characterized by an increase in some parameters such as number, mean lobule diameter and total glomic tissue volume when compared with age-matched controls, was observed in 23.8% of SIDS victims. Similar alterations have been reported in peripheral chemoreceptors of animals and human beings who are chronically hypoxemic. In SIDS, it could reflect an abnormal chemoreceptor function, contributing to an altered respiration control.

Carotid rupture and intraplaque hemorrhage: immunophenotype and role of cells involved.

BACKGROUND: A complete immunohistochemical characterization in complicated carotid plaques is still lacking. The cellular components of 165 carotid endarterectomy specimens were analyzed to assess their role in the pathogenesis of plaque rupture and intraplaque hemorrhage without rupture. METHODS AND RESULTS: The fibrous caps at the sites of plaque rupture showed CD68+ macrophages, T-lymphocytes, and scarce B-lymphocytes. Ruptured plaques showed mononuclear infiltrates in the caps, shoulders, and bases of the plaques in 85% of the cases. Only 46% of nonruptured plaques showed such infiltrates (P <.0001). Two types of lipid cores were recognized: avascular or mildly vascularized and highly vascularized. The vessels of the latter type reacted with CD31 and CD34. In 57.5% of the cases, the base and the shoulders of the plaques showed neoformed, CD34+ vessels, often surrounded by mononuclear infiltrates. Intraplaque hemorrhage without rupture had highly vascularized lipid cores in all cases. T-lymphocytes and macrophages were in close contact with neoformed vessels. CONCLUSIONS: Plaque rupture is characterized by mononuclear cell infiltration of the caps, whereas intraplaque hemorrhage without rupture is characterized by extensive vascularization of the plaque.

Cardiac involvement in acquired immunodeficiency syndrome--a review to push action. The Committee for the Study of Cardiac Involvement in AIDS.

As more effective therapies have produced longer survival times for human immunodeficiency virus (HIV)-infected patients, new complications of late-stage HIV infection including HIV-related heart disease have emerged. Almost any agent that can cause disseminated infection in patients with acquired immunodeficiency syndrome (AIDS) may involve myocardium, but clinical evidence of cardiac disease is usually overshadowed by manifestations in other organs, primarily the brain and lungs. Cardiac abnormalities are found at autopsy in two-thirds of patients with AIDS, and more than 150 reports of cardiac complications have been published. Cardiac involvement in HIV disease includes pericardial effusion, myocarditis, dilated cardiomyopathy, and/or endocardial involvement at any stage of the disease. This review deals with all the cardiac manifestations of AIDS and serves to highlight two problems and one indication. First of all, there are very few clinical studies. Current knowledge is based almost exclusively on echocardiography and autopsy studies. Observational or clinical trials would be useful. Second, there exists very poor information on the impact of treatment; and epidemiologic and clinicopathologic studies are mandatory for obtaining detailed data concerning the mechanisms of myocardial damage in AIDS. Finally, because cardiac complications are often clinically inapparent or subtle in the initial stages, periodic screening of HIV-positive patients by electrocardiogram and echocardiogram is probably indicated. In addition, AIDS may also provide the opportunity to gain insights into the pathogenesis of little understood cardiac diseases such as lymphocytic myocarditis and dilated cardiomyopathy.

Carotid atherosclerosis. Immunocytochemical analysis of the vascular and cellular composition in endarterectomies.

Papers dealing with rupture of carotid plaque surface are few in spite of the growing importance of the subject. The aim of this study was to analyze the cellular and vascular components of surgically excised carotid endarterectomies in order to obtain information about their role in the pathogenesis of the plaque rupture and intraplaque hemorrhage. Seventy-six surgical specimens of carotid endarterectomies were used for this study. The findings of immunophenotyping of the cellular constituents of the plaques were: 1) endothelial lining: the fibrous cap at the site of the rupture showed an eroded surface with loss of the endothelial lining. Conversely, in the remaining surface a continuous, not damaged row of endothelial cells stained with anti-CD31 and anti-CD34 was observed; 2) fibrous cap: the collagenous fibrous cap at the site of erosion was attenuated and the phenotypic characterization of the cells showed inflammatory components consisting mainly of macrophages (CD68 positive), 2/3 of the total infiltration. The remaining 1/3 was composed of T-lymphocytes and scarce B-lymphocytes. A close interaction between macrophages and capillaries and macrophages and T-lymphocytes was observed; 3) lipid cores: two different types of lipid cores could be depicted. Avascular or mildly vascularized lipid cores and highly vascularized, with neoformed vessels stained with CD34 and CD31. CD34 stained endothelia of all kind of vessels; conversely, neoformed vessels showed a weak stain with CD31. T-lymphocytes were found to be in close contact with neoformed vessels, and in some cases, migrating through the endothelial cells; 4) deeper layers of the plaque: the base and the shoulder of the plaques showed in 28/76 cases neoformed vessels, thin or thick walled, CD34 positive, generally surrounded by mild to extensive mononuclear infiltrates. Atherosclerotic plaques were found to belong to six different lesions: plaque rupture plus thrombosis (18/76, 23.6%), plaque rupture plus intraplaque hemorrhage plus thrombosis (18/76, 23.6%), intraplaque hemorrhage without plaque rupture (16/76, 21.0%), plaque rupture plus intraplaque hemorrhage (5/76, 6.5%), stable calcified non complicated plaque (14/76, 18.4%) and unstable, soft, non complicated plaque (5/76, 6.5%). The first four lesions were considered as "complicated lesions". Complicated plaques presented neoformed vessels in the periphery, shoulder and base of the plaque in 22/57 (38.5%) cases. Conversely only 1/14 (7.1%) of non complicated, stable calcified plaques presented neoformed vessels, (p < 0.05). Of note, the 5 causes of unstable, soft non complicated plaque presented neoformed vessels surrounding the plaque. In 10/57 (17.5%) complicated plaques unequivocal histological signs of old hemorrhages were found surrounding those vessels. Irrespective of presenting no rupture, 11/35 plaques showed a mononuclear infiltrate in the fibrous cap. In conclusion, rupture of carotid plaques (50% of the cases), is characterized by the presence of a macrophagic infiltration of the caps and by the direct apposition of T-lymphocytes to macrophages and a close relation of these cells to endothelial cells. This highly suggests a cell-to-cell interaction, which results in an inflammatory process. Intraplaque hemorrhage without rupture represented 21% of the endarterectomies. These lesions are not related to cap erosion, but to plaque vascularization. Most lipid cores were highly vascularized with neoformed vessels with macrophages and T-cells in close contact and in some cases disrupting the endothelium. The abrupt growing of the lipid core and/or an overproduction of oxygen free radicals could lead to the breakdown of core vessels and intraplaque hemorrhage.

Myocardial inflammatory infiltrate in human chronic chagasic cardiomyopathy: Immunohistochemical findings.

Chagas' disease is the most common form of chronic myocarditis in the world. It is characterized by a progressive chronic myocarditis that leads to cardiomegaly, arrhythmias, cardiac failure, and thromboembolic phenomena. This communication reports studies on the immunohistochemistry of chronic infiltrates in 30 endomyocardial biopsies and in contracting and specialized myocardium of autopsies of four patients suffering from Chagas' cardiomyopathy. Expression of the following antigens was studied: common leucocyte antigen (CLA-CD45R), L-26(CD20), CD68, kappa and lambda light chains and T-UCLH-1 (CD45RO), and MB-1. Streptavidin-peroxidase and streptavidin-alkaline phosphatase with biotinylated anti-mouse IgG were used as detection systems. Double immunostaining for the simultaneous demonstration of T lymphocytes (CD45R0) and macrophages was performed using both immunoenzymatic techniques consecutively. Expression of CD31 was detected for the demonstration of endothelial cells. In endomyocardial biopsies, tissue forms of trypanosomes were not found. The percentage of fibrous tissue was 24.1% ± 12.8% (range 8.2%-49%). Eosinophils were scarce (1/high-power field), but associated with necrotic areas of the myocardium. Mast cells were scarce or absent. They were always situated in fibrotic areas. The most remarkable finding was the presence of infiltrates consisting of macrophages and CLA-positive mononuclear cells. Twenty-six and one-half percent of them were T lymphocytes, and 10.5% were B lymphocytes. Lymphocytic infiltration was particularly associated with necrotic and degenerative myocardial lesions. Thirty percent of the infiltrate was composed of macrophages (positive CD68 cells). The remaining infiltrate was composed of mononuclear cells resembling macrophages and CLA-negative mononuclear cells. Contacts between CD68-positive cells and T lymphocytes were frequently found. CD31 antibodies clearly pointed out normal endothelial cells, in either normal or damaged vessels. No isolated cells positive for these antibodies were found within the mononuclear infiltrate. In autopsied hearts, myocardial lesions consisted of a chronic inflammatory process with fibrotic scars and extensive mononuclear infiltrates. No amastigote nests were found. A statistically significant difference (p < 0.05) was obtained when the percentage of fibrosis was compared in the specialized and contracting myocardiums (51.6% ± 18% vs. 43.4 % ± 8%). Eosinophils were scarce in infiltrates, reaching 5%, and they were associated with necrotic myocardium. Mast cells also were scarce or absent in specialized and in contracting myocardium. Almost all the lymphocytic population was T lymphocytes. Such infiltrates were more prominent in the working myocardium (39%) and in the specialized cells of the left branch of the His bundle than in the atrioventricular node and in the right Hisian branch (34.4%). The 31% of mononuclear cells were CD68 positive, thus corresponding to macrophages. Contacts among T lymphocytes and macrophages were frequently observed. Although much that is concerned with Chagas' cardiomyopathy is controversial, these may be the major ingredients for its pathogenesis: the parasite or a part of it, lymphocytes and macrophages, and fibrosis. Then a multifactorial or "combined theory" may be suggested to explain the sequence of events that lead to the chronic stage of the disease.

Cardiac extrinsic neuropathy: Lesions of the mediastinal paraganglia in chronic chagasic cardiomyopathy.

The pathology of cardiac innervation, both intrinsic and external to the heart (mediastinal paraganglia included), is scarcely known, yet it can be critical to life-threatening disorders in cardiac performance or to reflexes discharging outside the heart, or both. This article focuses on such a fundamental and ill-understood subject through an anatomoclinical outlook of mediastinal paraganglia lesions in the setting of sudden death in chronic chagasic cardiomyopathy.

Sudden cardiac death in the indeterminate phase of Chagas' disease associated with acute infarction of the right carotid body.

We recently came across a case of a patient in the indeterminate phase of Chagas' disease who died suddenly with cardiac arrhythmia associated with acute infarction of the right carotid body due to occlusive thrombosis in the glomic artery. Although the available data in this case do not offer definite evidence to support a cause-and-effect relationship between carotid body infarction and patient's sudden cardiac arrest, it is very likely that the acute infarction of the carotid body could be the distinct morphological counterpart of the functional disturbance. The infarction would affect the vagal-sympathetic interactions augmenting sympathetic action.

Scleroatrophy of the atrioventricular junctional specialized tissue (Lenegre-Lev Disease) in chronic chagas' heart disease.

This paper reports a case of bilateral bundle branch scleroatrophy and degeneration and upper interventricular septum crest fibrosis, often known as Lenegre-Lev disease, in chronic chagasic cardiomyopathy.

Histopathology of specialized and ordinary myocardium and nerves in chronic Chagas disease, with a morphometric study of inflammation and fibrosis.

Chagas disease, in the chronic phase, is known to be characterized by cardiac failure, and/or arrhythmias. To assess the involvement of the conduction system and of the working myocardium, morphometric and immunohistochemistry studies have been carried out on 4 autoptic hearts of chronic chagasic myocardiopathy. The characterization of interstitial infiltrates was performed by lymphocyte immunophenotyping with immunocytochemical techniques. These infiltrates were more prominent in the working myocardium and in the left branch of the His bundle. The infiltrates consisted of about 50% of macrophages and 50% of T-lymphocytes. Mast cells would not play a role in the chronic stages of the disease. Eosinophils were present in no more than the 5% of the inflammation. The fibrosis, especially of the conducting system seems to be facilitated by an impaired lymphatic outflow, whereas the evidence of neuroganglionic involvement was variable.