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Biomedical subjects

E R O'Brien

Publications and source records attributed to E R O'Brien.

26 records · Page 2Linked to original sources
PubMed1995

Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues.

Chlamydia pneumoniae TWAR has been associated with coronary heart disease by seroepidemiologic studies and direct detection of the organism in atheromatous lesions of coronary arteries and aorta. In this study, 38 fresh tissue specimens from patients with coronary artery lesions that were treated by directional coronary atherectomy were tested for C. pneumoniae. Twenty-three specimens were from patients with primary lesions and 15 were from patients with restenoses. C. pneumoniae was detected by polymerase chain reaction (PCR), immunocytochemical stain (ICC), or both in 20 of 38 specimens. Using cell identity markers, the organism was localized to macrophages. Ultrastructural evidence of the organism was found in the 2 specimens examined by transmission electron microscopy, which were also positive by both ICC and PCR. C. pneumoniae was found more frequently in tissues from restenoses than in primary lesions (P = .17). There was no relation between the frequency of detection of the organism and C. pneumoniae-specific antibody titers.

Adult↗
PubMed1995

In vitro susceptibility of human vascular wall cells to infection with Chlamydia pneumoniae.

Chlamydia pneumoniae is a common respiratory pathogen. Recent studies have demonstrated the presence of C. pneumoniae in coronary and aortic atherosclerotic lesions. To study the role of C. pneumoniae in atherosclerosis, we investigated the susceptibilities of three different cells of the human vascular wall to infection with C. pneumoniae AR-39. These cell types were endothelial cells, smooth muscle cells, and macrophages derived from peripheral blood monocytes. Infection was assessed by using a direct fluorescent antibody to assess inclusion counts. Duplicate cell samples were harvested 3 days postinfection and were passed in HL cells, a susceptible human epithelial cell line, to determine if infectious organisms were produced. Endothelial cells, smooth muscle cells, and macrophages were capable of supporting C. pneumoniae growth in vitro. These results showed that three different cell types known to be important in atherogenesis are susceptible to infection with C. pneumoniae.

Cells, Cultured↗
PubMed1995

Expression of thrombospondins by endothelial cells. Injury is correlated with TSP-1.

The thrombospondins (TSP-1, -2, and -3) comprise a family of proteins that are homologous at the carboxy terminus but have unique sequences at the amino terminus that might be correlated with the regulation of cell behavior. To investigate the expression of TSP-1, -2, and -3 in endothelial cells, we examined developing murine blood vessels and human atherosclerotic plaques by in situ hybridization. The expression of TSP-1 was also characterized in cultured bovine aortic endothelial cells. Expression of TSP-2 was seen in the dorsal aorta as early as embryonic day 10; TSP-1 was not detected in endothelial cells until later stages, and TSP-3 was not apparent in the vasculature. In atherosclerotic specimens, TSP-1 mRNA was detected in many intraplaque microvessels and in the endothelium lining the atheromatous plaque; TSP-2 was absent from these regions. Cultured bovine aortic endothelial cells did not transcribe TSP-2 mRNA at detectable levels. There were high steady-state levels of TSP-1 mRNA in subconfluent bovine aortic endothelial cells before confluence and at the wound edge after injury of the cell monolayer, with maximal expression of TSP-1 in cultures at a time during which approximately 35% of the cells were in S phase. As the majority of these cells subsequently undergo mitosis, these data are consistent with TSP-1 as an inhibitor of endothelial cell proliferation that functions in G1. These results support the conclusion that, despite sequence homology, the TSPs have distinct functions in vascular biology.

Animals↗
PubMed1994

Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques.

How an atherosclerotic plaque evolves from minimal diffuse intimal hyperplasia to a critical lesion is not well understood. Cellular proliferation is a relatively infrequent and modest event in both primary and restenotic coronary atherectomy specimens, leading us to believe that other processes, such as the formation of extracellular matrix, cell migration, neovascularization, and calcification might be more important for lesion formation. The investigation of proteins that are overexpressed in plaque compared with the normal vessel wall may provide clues that will help determine which of these processes are key to lesion pathogenesis. One such molecule, osteopontin (OPN), is an arginine-glycine-aspartate-containing acidic phosphoprotein recently shown to be a novel component of human atherosclerotic plaques and selectively expressed in the rat neointima following balloon angioplasty. Using in situ hybridization and immunohistochemical methods, we demonstrate that in addition to macrophages, smooth muscle and endothelial cells synthesize OPN mRNA and protein in human coronary atherosclerotic plaque specimens obtained by directional atherectomy. In contrast, OPN mRNA and protein were not detected in nondiseased vessel walls. Furthermore, extracellular OPN protein collocalized with sites of early calcification in the plaque that were identified with a sensitive modification of the von Kossa staining technique. These findings, combined with studies showing that OPN has adhesive, chemotactic, and calcium-binding properties, suggest that OPN may contribute to cellular accumulations and dystrophic calcification in atherosclerotic plaques.

Aged↗
PubMed1994

Angiogenesis in human coronary atherosclerotic plaques.

Neovascularization in the walls of coronary arteries is associated with the presence of atherosclerotic plaque. The mechanisms responsible for the formation of these intraplaque microvessels are not understood. The purpose of this study is to examine the prevalence of endothelial cell replication in plaque microvessels. Two hundred and one primary and restenotic coronary atherectomy specimens were analyzed for the presence of microvessels and proliferation as reflected by positive immunolabeling for Ulex agglutinin and the proliferating cell nuclear antigen, respectively. In primary but not restenotic specimens, proliferation of any cell type was associated with the detection of microvessels on the same slide. However, intraplaque microvessels were more commonly found in restenotic compared to primary specimens (P = 0.004). Twelve highly vascularized specimens with evidence of replication were subjected to detailed histomorphological and quantitative image analyses. At 200 x, the most vascular optical field of each slide was identified and consistently included plaque macrophages. Total slide endothelial cell replication indices for these specimens varied, but in some instances were remarkably elevated (eg, 43.5%). The role of intraplaque angiogenesis may be analogous to that of tumor or wound angiogenesis and be important in development and progression of coronary artery lesions and restenosis.

Atherectomy, Coronary↗
PubMed1993

Proliferation in primary and restenotic coronary atherectomy tissue. Implications for antiproliferative therapy.

On the basis of animal models of arterial injury, smooth muscle cell proliferation has been posited as a dominant event in restenosis. Unfortunately, little is known about this proliferation in the human restenotic lesion. The purpose of this study was to determine the extent and time course of proliferation in primary and restenotic coronary atherectomy-derived tissue. Primary (n = 118) and restenotic (n = 100) coronary atherectomy specimens were obtained from 211 nonconsecutive patients. Immunocytochemistry for the proliferating cell nuclear antigen (PCNA) was used to gauge proliferation in the atherectomy specimens. The identity of PCNA-positive cells was then determined using immunohistochemical cell-specific markers. Eighty-two percent of primary specimens and 74% of restenotic specimens had no evidence of PCNA labeling. The majority of the remaining specimens had only a modest number of PCNA-positive cells per slide (typically < 50 cells per slide). In the restenotic specimens, PCNA labeling was detected over a wide time interval after the initial procedure (eg, 1 to 390 days), with no obvious proliferative peak. Cell-specific immunohistochemical markers identified primary and restenotic PCNA-positive cells as smooth muscle cells, macrophages, and endothelial cells. In conclusion, the findings were as follows: (1) Proliferation in primary and restenotic coronary atherectomy specimens, as indicated by PCNA labeling, occurs infrequently and at low levels. (2) The response to injury in existing animal models of angioplasty may follow a very different course of events from the clinical reality in human atherosclerotic coronary arteries and may help explain why current approaches to restenosis therapy have been ineffective.

Adult↗