CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease

The pathogenesis of coronary arterial inflammation in acute Kawasaki disease (KD) is unclear. To test the hypothesis that the KD vascular lesion is an activated T lymphocyte-dependent process, immunohistochemical studies were done on coronary artery aneurysms from 8 fatal acute KD cases by using antibodies to CD45RO (activated or memory T lymphocyte), CD8 (cytotoxic T lymphocyte), CD4 (helper T lymphocyte), HAM56 (macrophage), and CD20 (B lymphocyte). Acute KD coronary arteritis was characterized by transmural infiltration of CD45RO T lymphocytes with CD8 T lymphocytes predominating over CD4 T lymphocytes. Macrophages were present primarily in the adventitial layer; B lymphocytes were notably absent. These data lend support to the hypotheses that KD results from infection with an intracellular pathogen, such as a virus, whose antigens are presented by major histocompatibility complex class I molecules, and that CD8 T lymphocytes and macrophages are important in the pathogenesis of KD coronary aneurysms.     

CD40-CD154 expression in calcified and non-calcified coronary lesions of patients with chronic renal failure

The high incidence of cardiovascular complications in patients with chronic renal failure (CRF) is partly explained by more aggressive atherosclerosis, i.e. increased incidence and severity of lesions with higher tendency to calcification. The pathogenesis of this accelerated atherosclerosis, however, is not completely understood. Among other risk factors, chronic micro-inflammation may be involved. Activation of cells and adhesion molecules in atherosclerosis is governed by CD40-CD154 (CD40 ligand) interaction. Therefore, we investigated the expression and distribution of CD40-CD154 in different coronary atherosclerotic lesions of CRF patients and non-renal control patients. Coronary plaques of 57 patients with and without CRF were categorized according to the Stary classification and analysed for in situ protein expression of CD40, CD154 and CRP using immunohistochemistry and a semiquantitative scoring system. The nature, number and distribution of infiltrating cells was analysed and correlated to the types of coronary lesions and in particular to the presence of calcification. CD40 was over expressed in media myocytes of coronary plaques of both uremic and control patients. Inside the plaques, CD40 was expressed on endothelial cells, T lymphocytes, macrophages, fibroblasts, and smooth muscle cells. CD154 expression was seen on T cells in areas densely infiltrated by CD40 positive macrophages. In uremic and control patients higher in situ expression of CD40, CD154 and CRP was seen in calcified compared to non-calcified lesions. Inside the plaques, there were significant differences in the expression pattern of CD40 and CD154 between uremic and control patients. In addition, in uremic patients coronary plaques showed higher CRP protein expression compared to control patients. The data indicate a higher inflammatory status of coronary lesions as well as involvement of the CD40-CD154 signaling cascade in CRF patients, especially in cases of calcified atherosclerotic lesions.     

Immunohistochemical observations on cellular response in unilocular hydatid lesions and lymph nodes of cattle

As we believe the immunohistochemistry of the hydatid lesions and draining lymph nodes has never been studied, we collected them from the liver and lungs of cattle in Uruguay for such a study. Frozen sections of the tissues were immunohistochemically stained using monoclonal antibodies against surface markers CD2, CD4, CD5, CD8, B cell and granulocyte-monocyte/macrophage and antiserum against specific granules of bovine eosinophils. The adventitial layer of the cyst wall consists of a layer of epithelioid cells and connective tissue. The cells from the epithelioid cell layer were a kind of macrophage. In most cases having progressive hydatid cysts, CD8+ cells were predominant in the pericystic adventitia, and a relatively small number of CD4+ cells were in the same area. In the adventitial layer surrounding the regressive and involutional hydatid cysts, infiltrating lymphocytes were composed mostly of CD4+ cells. An eosinophil-mediated destruction of the laminated layer was recognized in the regressive and involuted hydatid cysts. The subpopulations of T cells in the local lymph nodes tended to be similar to T cells in the adventitial layer of hydatid lesions. From our findings, we consider that infiltration of eosinophils and the subpopulations of lymphocytes infiltrating the hydatid lesions in the liver and lungs are derived from cells in the draining lymph nodes of both organs.     

Immunohistologic study on focal lymphocytic infiltration in the liver of the elderly autopsy cases

Immunologic and immunohistologic analyses were performed on lymphocytic infiltration in periportal areas of the liver obtained from 105 autopsy cases over 60 years of age and 63 cases under 60 years of age, all cases showing no symptoms of overt liver diseases. Lymphocytic infiltration in the periportal areas began to be found in the livers of young autopsy cases in the 4th decade, with an incidence of more than 60%. The incidence reached 100% in cases of 6th decade and over, accompanied by increased severity. The infiltrating lymphocytes consisted mainly of T cells, (approximately 85%), regardless of sex, age and underlying diseases. In terms of T cell subsets composing the infiltrating lymphocytes, there were 3 types; A:CD4+ cells greater than CD8+ cells. B:CD4+ cells = CD8+ cells. C:CD4+ cells greater than CD8+ cells. Type A was seen in 60/105 cases (57%), type B in 10/105 (9%) and type C in 35/105 (34%). The presence of cases with predominant CD8+ cells appeared to be characteristic of lymphocytic infiltration lesions in the liver, and was different from lesions in other organs. It was suggested that lesion of lymphocytic infiltration in the periportal areas of the liver might be of an autoimmune nature, gradually advancing with age.     

Pro-atherogenic alterations in T-lymphocyte subpopulations related to acute hyperglycaemia in type 2 diabetic patients.

BACKGROUND: T cells are among the earliest cells to infiltrate the arterial intima during the initial stages of atherosclerosis. Alterations in the peripheral blood lymphocyte distribution might be associated with intensive lymphocytes extravasation and stimulation of atherosclerotic plaque development. Epidemiological data reveal that short-term postprandial hyperglycemia is a significant risk factor for coronary heart disease. Using a parameter that indicates recently-past acute hyperglycemia, 1,5-anhydro-D-glucitol (1,5-AG), the aim of the present study was to elucidate which alterations in peripheral blood T-lymphocytes, if any, are associated with acute hyperglycemia in patients with type 2 diabetes mellitus (DM) and, thus, might be involved in the progression of atherosclerosis. METHODS AND RESULTS: Measurement of fasting glucose level, glycated hemoglobin A(1c), 1,5-AG, lipid profile and lymphocyte receptors expression (CD3+, CD4+, CD8+, CD8+28+, CD+28 -) was performed in 97 patients with type 2 DM, 23 patients with coronary heart disease, and 15 healthy controls. The mean CD3+, CD4+, CD8+28 - and CD8+28+ lymphocyte counts were significantly higher in the DM patients than in both control groups. Multiple regression analysis revealed that CD4+ and CD8+28- lymphocyte counts primarily were dependent on 1,5-anhydro-D-glucitol plasma levels. CONCLUSIONS: These results suggest that acute hyperglycemia results in the progression of atherosclerosis in type 2 DM, at least in part through changes in CD4+ and CD8+28- lymphocyte subsets.     

树突状细胞在动脉粥样硬化中的作用

基础和临床研究均证实,炎症反应在动脉粥样硬化(atherosclerosis,AS)的发生、发展及其导致的临床事件过程中起着重要作用.在发生AS的血管内膜和粥样斑块中可见T淋巴细胞、巨噬细胞以及树突状细胞(dendritic cell,DC)聚集现象.作为激活T淋巴细胞最主要的抗原提呈细胞,DC具有决定T淋巴细胞活化、凋亡以及聚集等的重要功能.文章就DC与AS病变的相关性进行了综述.     

The role of T-lymphocyte subpopulations in acute myocardial infarction

T lymphocytes have the potential to affect atherosclerosis at different stages of the process. They play an active role in acute myocardial infarction (AMI) and myocardial damage, and may affect the clinical outcome of patients with coronary artery disease. CD40 ligand expression on T lymphocytes promotes the expression of matrix-degrading enzymes in vascular smooth muscle cells and may thus establish a new pathway of immune-mediated destabilization of the human atheroma. The major class of T lymphocytes present in atherosclerotic lesions is CD4+. CD4+ cells differentiate into Th1 and Th2 lineage in response to the local milieu of cytokines. Much of the emphasis in atherosclerosis research is focused on the role of Th1 type responses.     

肺功能正常吸烟者和慢性阻塞性肺疾病患者肺腺泡动脉炎症特征

目的 研究肺功能正常吸烟者和慢性阻塞性肺疾病(COPD)患者肺腺泡动脉炎症的病理特点。方法 取手术切除的远离周围型肺癌的正常肺组织,分肺功能正常不吸烟组(A组,10例)、肺功能正常吸烟组(B组,13例)、吸烟COPD稳定期组(C组,10例),比较3组肺腺泡动脉病理结构改变、炎性细胞在非肌型动脉(NMA)、部分肌型动脉(PMA)外膜,肌型动脉(MA)内、中、外膜的浸润水平,并分析其与临床指标的相关性。结果 (1)B组(32.7±7.7)、C组(37.4±4.5)较A组(24.4±5.0)MA比例增高,MA内、中膜增厚,C组MA外膜胶原纤维增生,面积明显增大。(2)B组和C组CD+45白细胞、CD3+总T淋巴细胞、CD8+T淋巴细胞在各型肺腺泡动脉表达的范围和程度均较A组增高,以CD8+T淋巴细胞增高为主,炎性细胞浸润以肺腺泡NMA最为明显,在MA以外膜最显著,且C组较B组明显;而CD4+T淋巴细胞、B淋巴细胞、巨噬细胞、中性粒细胞在3组各型肺腺泡动脉浸润程度比较差异均无统计学意义(P值均＞0.05)。(3)CD45+白细胞、CD3+总T淋巴细胞、CD8+T 淋巴细胞在MA的浸润程度与MA管壁厚度、吸烟指数呈正相关,与第1秒用力呼气容积占预计值百分比呈负相关,CD3+总T淋巴细胞、CD8+T淋巴细胞浸润程度与BODE指数呈正相关,CD8+T淋巴细胞浸润程度与6 min步行距离呈负相关。结论 肺功能正常吸烟者和COPD患者均已出现以CD8+T 淋巴细胞浸润为特征的同性质炎症反应,炎症累及各型肺腺泡动脉,肺动脉炎症是影响COPD临床病程发展的重要因素之一。     

Off-pump coronary artery bypass grafting does not reduce lymphocyte activation

OBJECTIVE: In this study, we test the hypothesis that off-pump coronary bypass surgery might result in less lymphocyte activation than on-pump coronary surgery. We also study the behavior of lymphocyte activation markers during and after surgery. BACKGROUND: Coronary artery bypass surgery is known to be associated with changes of inflammatory mediators, immune function, and early phase lymphocyte activation, which could cause postoperative lymphopenia and lymphocyte unresponsiveness. METHODS: We studied lymphocyte activation response in 28 patients randomized to off-pump (n = 13) or on-pump (n = 15) coronary artery bypass surgery. Expression of CD25, CD26, CD69, and DR on T (CD3+) and B (CD19+) lymphocytes on peripheral blood was assessed through flow cytometry. RESULTS: The response of T lymphocytes and their activation markers, as well as B lymphocytes and their activation markers, was similar after on- and off-pump surgery. Overall, T lymphocytes decreased to the lowest level 9 h after surgery and tended to increase later. For B lymphocytes, there was early reduction with increase on the 1st postoperative day. There was early activation of CD69+ and late activation of CD25+ on T lymphocytes. For B lymphocytes, there was early activation of CD69+ and late activation of DR+. CONCLUSIONS: (1) Compared to on-pump cardiopulmonary bypass, off-pump surgery does not reduce lymphocyte activation. (2) Coronary bypass surgery causes the early activation of lymphocytes, as evidenced by the increased expression of lymphocyte activation markers.     

CD68-阳性巨噬细胞在人冠状动脉粥样硬化病变中的分布特点及其意义

目的 探讨人冠状动脉粥样硬化病变中CD68-阳性巨噬细胞的分布以及与冠状动脉粥样硬化病变类型、管腔狭窄之间的关系及其意义.方法 选用53例尸检病例的312块冠状动脉组织标本,光镜下诊断弥漫性内膜增厚和冠状动脉粥样硬化病变及其类型,用免疫组织化学计数冠状动脉粥样硬化病变中CD68-阳性巨噬细胞,用Scion图像软件系统检测和计算冠状动脉标本中管腔狭窄程度、脂质坏死核心和钙化基质面积.结果 在冠状动脉粥样病变中, 40% (124/312)为弥漫性内膜增厚, 5% (16/312)为Ⅰ型, 10% (31/312)为Ⅱ型, 21% (66/312)为Ⅲ型, 4% (14/312)为Ⅳ型, 18% (55/312)为Ⅴ型和2% (6/312)为Ⅵ型.脂质坏死核心面积在高胆固醇组明显大于正常胆固醇组(P<0.05),而钙化基质面积在早期病变(Ⅰ～Ⅲ型)和进展期病变(Ⅳ～Ⅵ型)之间有显著性差异(P<0.05);冠状动脉粥样硬化病变CD68-阳性巨噬细胞随着冠状动脉粥样硬化病变进展和管腔狭窄程度的加重而增多,分别呈正相关(P<0.01),且不同病变类型、管腔狭窄程度之间以及正常胆固醇组与高胆固醇组之间有显著性差异(P<0.05).结论 CD68-阳性巨噬细胞随着人冠状动脉粥样硬化病变进展和管腔狭窄程度的加重而增多,表明巨噬细胞浸润始终始发和加重冠状动脉粥样硬化病变,大量巨噬细胞主要在斑块肩部区浸润和脂质坏死核心的增大与冠状动脉粥样硬化病变进展、不稳定性斑块破裂及并发症的发生有关.     

Immunoglobulin stabilizes plaque formation in experimental atherosclerosis

OBJECTIVES: Immunoglobulin treatment is known to suppress atherosclerosis in apolipoprotein E-deficient mice. In addition, immunoglobulin inhibits atherosclerosis via the Fc receptors. However, the effect of immunoglobulin treatment at the advanced stage of atherosclerosis is still unclear. This study examined the effects of immunoglobulin on apolipoprotein E-deficient mice at the advanced stage of the disease. METHODS: Atherosclerosis was induced in mice fed a high-fat diet containing 0.3% cholesterol. After confirming the presence of atherosclerotic lesions at 11 weeks, mice were intraperitoneally treated with injections of either intact type of immunoglobulin (1 g/kg/day) or F (ab') 2 fragments of immunoglobulin (1 g/kg/day) on alternate days over 4 weeks. Oil red-O staining and immunohistochemical staining with CD4+ cells were performed of the aorta, and atherosclerotic lesions was evaluated and compared between the groups. RESULTS: Fatty streak lesion was significantly suppressed by intact immunoglobulin compared with saline, and inflammatory cell infiltration and expression of CD4+ cells were less in mice treated with intact immunoglobulin compared with the control. CONCLUSIONS: Immunoglobulin treatment even at the advanced stage of atherosclerosis suppressed the development of fatty lesions and may stabilize atherosclerotic plaques by inhibiting inflammatory cell expression. Immunoglobulin suppression of atherosclerosis was confirmed to act via the Fc receptors.     

Inflammatory rheumatic disease and smoking are predictors of aortic inflammation: a controlled study of biopsy specimens obtained at coronary artery surgery

OBJECTIVE: Several inflammatory rheumatic diseases are associated with accelerated atherosclerosis. Atherosclerosis may result from systemic and/or local vascular inflammation. The aim of this study was to evaluate the occurrence of chronic inflammatory infiltrates in the aortas of patients with and those without inflammatory rheumatic disease who had undergone coronary artery bypass graft (CABG) surgery, and to assess the relationship between the infiltrates and other factors thought to play a role in atherosclerosis, such as smoking. METHODS: Aortic specimens routinely removed during CABG surgery in 66 consecutive patients with inflammatory rheumatic disease and 51 control patients without inflammatory rheumatic disease were examined by light microscopy for the occurrence, location, and severity of chronic inflammatory infiltrates and atherosclerotic lesions. RESULTS: Mononuclear cell infiltrates in the inner adventitia (apart from those localized along the epicardium) were more frequent in the group of patients with inflammatory rheumatic disease (47% versus 20%; P = 0.002, odds ratio [OR] OR 3.6, 95% confidence interval [95% CI] 1.6-8.5), and the extent of these infiltrates was greater. Multivariate analyses revealed that the occurrence of mononuclear cell infiltrates was associated with inflammatory rheumatic disease (OR 2.99, P = 0.020) and current smoking (OR 3.93, P = 0.012), and they were observed in 6 of 7 patients with a history of aortic aneurysm. Inflammatory infiltrates in the media were seen only in patients with inflammatory rheumatic disease. The frequency of atherosclerotic lesions, inflammation within the plaques, and epicardial inflammatory infiltrates in the 2 groups was equal. CONCLUSION: Among aortic samples collected during CABG surgery, those obtained from patients with inflammatory rheumatic disease had more pronounced chronic inflammatory infiltration in the media and inner adventitia than those obtained from control patients. Current smoking was an independent predictor of chronic inner adventitial infiltrates. The infiltrates may represent an inflammatory process that promotes atherosclerosis and formation of aneurysms.     

Histololfic analysis of directional coronary atherectomy samples: A review of findings and their clinical relevance

Histologic analysis of atherectomy samples from >400 patients who received directional coronary atherectomy at 3 separate institutions disclosed 2 major categories of tissue: atherosclerotic plaque (with or without thrombus) and intimal proliferation (hyperplasia, with or without thrombus). The predominant tissue type in atherectomy samples from native, primary, or de novo coronary artery stenoses was atherosclerotic plaque. The predominant tissue type in atherectomy samples from restenosis lesions (prior balloon angioplasty, atherectomy, or both) was intimal proliferation with variable amounts of atherosclerotic plaques (with or without thrombus). Deep vessel wall components (media, adventitia) were identified at varying frequencies. The clinical relevance of atherectomy tissue is reviewed.     

Immunohistochemical investigation of hepatitis B virus associated antigens, HLA antigens and lymphocyte subsets in type B chronic hepatitis

HLA antigens, hepatitis B virus (HBV)-associated antigens and lymphocyte subsets in liver tissue from 35 patients with HBs antigenemia were studied using an immunoperoxidase double staining method and immunoelectron microscopy in order to clarify the immune mechanism of hepatocyte lysis in type B hepatitis. Immune light and electron microscopy using monoclonal antibodies to lymphocyte subsets revealed that infiltrating lymphocytes in the areas of piecemeal necrosis and focal necrosis were predominantly CD8-positive, showing direct contact with hepatocytes. In contrast, CD4(+) cells were infrequently observed in necrotizing inflammatory lesions. HLA-A,B,C antigens were mainly found on hepatocytes in areas of piecemeal necrosis and focal necrosis, in association with CD8(+) lymphocyte infiltration. HLA-DR antigens were demonstrated on a few hepatocytes in the same lesions. In cases of CAH with serum HBeAg positive, HLA-A,B,C, antigens and HBV antigens simultaneously demonstrated on the same hepatocytes. Especially, hepatocytes expressing both HLA-A,B,C antigen and HBsAg on the plasma membrane showed direct contact with CD8(+)lymphocytes. This finding fulfilled the morphological requirements for HBsAg as a target antigen. On the other hand, HBcAg was hardly demonstrated in the liver cell membrane but was demonstrated mainly in the cytoplasm. Compared with the nuclear localization of HBcAg in cases of NSR, cytoplasmic localization of this antigen may be associated with membranous expression of new antigens induced by HBV infection.     

Immunohistochemical investigation of hepatitis B virus associated antigens,HLA antigens and lymphocyte subsets in type B chronic hepatitis

HLA antigens, hepatitis B virus (HBV)-assodated antigens and lymphocyte subsets in liver tissue from 35 patients with HBs antigenemia were studied using an immunoperoxidase double staining method arid immunoelectron microscopy in order to clarify the immune mechanism of hepatocyte lysis in type B hepatitis. Immune light and electron microscopy using monoclonal antibodies to lymphocyte subsets revealed that infiltrating lymphocytes in the areas of piecemeal necrosis and focal necrosis were predominantly CD8-positive, showing direct contact with hepatocytes. In contrast, CD4(+) cells were infrequently observed in necrotizing inflammatory lesions. HLA-A,B,C antigens were mainly found on hepatocytes in areas of piecemeal necrosis and focal necrosis, in association with CD8(+) lymphocyte infiltration. HLA-DR antigens were demonstrated on a few hepatocytes in the same lesions. In cases of CAH with serum HBeAg positive, HLA-A,B,C, antigens and HBV antigens simultaneously demonstrated on the same hepatocytes. Especially, hepatocytes expressing both HLA-A,B,C antigen and HBsAg on the plasma membrane showed direct contact with CD8(+) lymphocytes. This finding fullfilled the morphological requirements for HBsAg as a target antigen. On the other hand, HBcAg was hardly demonstrated in the liver cell membrane but was demonstrated mainly in the cytoplasm. Compared with the nuclear localization of HBcAg in cases of NSR, cytoplasmic localization of this antigen may be associated with membranous expression of new antigens induced by HBV infection.     

T cells and cytokines in atherogenesis

Recent findings suggest that inflammation plays a key role in atherosclerosis from the earliest stage of lesion initiation, to the ultimate complication of thrombosis. In patients who died because of acute coronary syndromes (ACS), coronary atherosclerotic plaques are characterized by the presence of macrophages, and to a lesser extent T-lymphocytes, at the immediate site of either plaque rupture or superficial erosion. The rupture-related inflammatory cells are activated, indicating ongoing inflammation. ACS patients are also characterized by activated circulating lymphocytes, monocytes and neutrophils, and by increased concentrations of proinflammatory cytokines and of the highly sensitive acute phase reactant C-reactive protein. Interestingly, an unusual subset of T cells, CD4+ CD28null T cells, involved in vascular complication of rheumatoid arthritis because of their functional profile predisposing for vascular injury, are expanded in the peripheral blood and infiltrate the coronary lesions of ACS patients. The presence of activated T lymphocytes implies antigenic stimulation, but the nature of such antigen(s) remains to be investigated. Several autoantigens expressed in the atherosclerotic plaque, including oxidized LDL and heat shock proteins, and infectious agents are able to elicit an immune response. The inflammatory component is not localized to the 'culprit' plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium.     

Characterisation of progenitor cells in human atherosclerotic vessels

Recent data from animal models has demonstrated that both endothelial and smooth muscle progenitor cells contribute to the development of atherosclerosis. However, no data exists concerning the presence of progenitor cells in human atherosclerotic vessels. In the present study, a range of normal and atherosclerotic human arteries were collected from patients undergoing coronary artery bypass surgery. Segments of internal mammary artery (normal controls), and segments of proximal ascending aorta with visible fatty streak were analysed. Immunofluorescence was used to detect a panel of progenitor cell markers. A small number of progenitor cells were identified within neointimal lesions and the adventitia with variable expression of CD34, stem cell antigen (Sca-1), c-kit and VEGF receptor 2 (VEGFR2) markers, but no CD133 expression. On average there was a two- to three-fold increase in progenitor cell number in the adventitia of atherosclerotic vessels compared with normal controls, with a significant difference (p<0.05) in the frequency of cells expressing VEGFR2. Thus, we have provided the first evidence that vascular progenitor cells exist within atherosclerotic lesions, and identified an increased number of progenitor cells in the adventitia of human atherosclerotic vessels. These cells might be a source for smooth muscle cells (SMCs), macrophages and endothelial cells (ECs) that form atherosclerotic lesions.     

Cytokine profiles and T cell function in acute coronary syndromes

AIMS: In advanced human atherosclerotic plaques infiltrating T cells congregate at sites of plaque rupture. However, little is known about the systemic activation of circulating T cells in acute coronary syndromes as a prerequisite for recruitment to atherosclerotic lesions. METHODS AND RESULTS: As a measure for specific lymphocyte activation we analyzed IFN-gamma production of T cells after stimulation with a superantigen and expression of CXCR-3 and CCR-3 in patients with acute myocardial infarction (AMI), unstable angina (uAP) or stable angina (sAP). Furthermore, concentrations of the circulating cytokines interleukin (IL)-1, IL-6, IL-1beta, IL-12 p70 and RANTES that modify T cell function were measured. In uAP an increased Th1 and a decreased Th2 response was identified by enhanced interferon-gamma generation of T lymphocytes, increased levels of IL-1beta, IL-12 p70 and RANTES and decreased expression of CCR3. In AMI a systemic inflammatory reaction predominates with enhanced expression of the early activation marker CD69 on T lymphocytes and elevated levels of IL-6 and IL-10 that suppress Th1 activation. CONCLUSION: Interferon-gamma production of activated T cells in acute coronary syndromes may, therefore, be governed by the release of specific pro- and anti-lymphocyte activating cytokines.     

Cardiovascular pathology in hyperlipoproteinemia. Anatomic observations in 42 necropsy patients with normal or abnormal serum lipoprotein patterns

Certain clinical and cardiovascular necropsy findings are described in 28 patients with known hyperlipoproteinemia and 14 patients known to have a normal lipoprotein pattern. Of the 42 patients, 28 had symptomatic ischemic heart disease: 20 of these had hyperlipoproteinemia (9 type II, 2 type III, and 9 type IV), and 8 had a normal lipoprotein pattern. The average age at death in the 20 patients with hyperlipoproteinemia and symptomatic ischemic heart disease was 48 years, and in the 8 with a normal lipoprotein pattern and ischemic heart disease, 46 years. The degree of coronary arterial luminal narrowing was severe in all patients with ischemic heart disease whether their lipoprotein pattern was normal or abnormal. In all 28 patients with symptomatic ischemic heart disease, the lumen of at least 1 of the 3 major coronary arteries was narrowed more than 75 percent by old atherosclerotic plaques, and in 25 of these all 3 major coronary arteries were narrowed to this extent. With the exception of 1 of the 2 patients with a type III pattern, the composition of the coronary atherosclerotic plaques was similar among patients with type II, III and IV hyperlipoproteinemia and among those with a normal lipoprotein pattern. Attention is called to the unique type of valvular aortic stenosis that frequently develops in the homozygote with a type II pattern and also to the reversed distribution of the aortic atherosclerotic plaquing in the homozygote with a type II pattern. In these patients the amount of plaquing appears to be greater in the ascending than in the abdominal portion of the aorta. Lipid plaques were observed on left atrial endocardium in 2 patients: One had type I hyperlipoproteinemia without associated coronary or aortic atherosclerosis; the second had a type III pattern with extensive coronary and aortic atherosclerosis. These left atrial endocardial lipid deposits may be unique to these hyperlipoproteinemias. In conclusion, it appears clear that atherosclerosis is accelerated or occurs prematurely in patients with type II, III and IV hyperlipoproteinemia, but that hyperlipoproteinemia is not a prerequisite for premature development of severe atherosclerosis.