Heterogeneity of Coronary Plaque Morphology and Natural History: Current Understanding and Clinical Significance

Purpose of Review

Despite the important progress in identifying high-risk atherosclerotic plaques, many key elements are elusive. Advanced imaging modalities provide valuable information about the anatomic and functional plaque characteristics and underscore the presence of multiple plaque morphologies. However, how the heterogeneity of atherosclerotic plaque can alter our current understanding of coronary artery disease is not fully understood.

Recent Findings

Along the length of an individual plaque, the morphology patterns display marked heterogeneity. Contrary to previous beliefs, plaque morphology is also highly dynamic over time, with the vast majority of high-risk plaques becoming quiescent and mild plaques becoming severely obstructive in a short period of time. Endothelial shear stress, a local hemodynamic factor known for its critical effects in plaque initiation and progression, also displays longitudinal heterogeneity contributing to the arterial wall response in all time points.

Summary

Risk stratification of plaques based on the morphological characteristics at one region of the plaque, usually the minimal lumen diameter, and at one point in time may be misleading. The evaluation of both morphological and hemodynamic characteristics along the length of a plaque will improve the risk assessment of individual plaques.

     

The role of cytokines in polymyositis

Objective. To investigate the effect of interferon-γ (IFNγ) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro. Methods. Human muscle cell cultures were established from normal muscle biopsy material, using the explant technique. T cells were studied for their capacity to adhere to IFNγ-treated and untreated myoblasts and myotubes. The role of intercellular adhesion molecule type 1 (ICAM-1) in cell adhesion to muscle cells was examined in blocking studies, by enzyme-linked immuno-sorbent assay (ELISA), and by immunohistochemical staining using monoclonal antibodies (MAb). Results. Treatment of muscle cells (myoblasts and myotubes) with IFNγ resulted in a significant dose-dependent increase in the number of adherent T cells. Adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM-1 and to lymphocyte function–associated antigen type 1, but not by MAb to HLA–DR. There was no difference in the level of T cell adhesion to IFNγ-treated allogeneic versus autologous muscle cells. By ELISA and immunohistochemical analysis, ICAM-1 expression on the surface of cultured human muscle cells was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFNγ. Conclusion. Induction of cell adhesion molecules on muscle cells by IFNγ may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.     

The utility of a measure of aggression in differentiating abusing parents from other parents who are experiencing familial disturbance

Discussed the utility of a measure of aggression using the MMPI (N = 54). Although child abusers significantly differed from a distressed and socioeconomic-status matched group on this scale, a discriminative analysis on the scale failed to adequately differentiate the groups. Results are discussed in terms of the deficiences in the current method of separating their groups and for constructing measures that are likely to differentiate aggressive from nonaggressive populations.     

A new model for studying eosinophil migration across cultured intestinal epithelial monolayers

OBJECTIVE: Eosinophils play an important role in some gastrointestinal inflammatory conditions. Stimulated eosinophils migrate across the vascular endothelial wall and into the intestinal epithelium where by-products such as proteases may contribute to intestinal epithelial damage. Little is known about the epithelial migration of the eosinophils in the gut. The lack of data is attributable in part to the scarcity of human eosinophils for studies. HL-60-differentiated eosinophils present a means to perform studies on eosinophil function and chemotaxis. HL-60 clone 15 can be induced to differentiate into cells closely resembling human eosinophils. The authors describe a novel model for studying eosinophil migration across the intestinal epithelium. METHODS: Fluorescent-labeled HL-60 eosinophils were incubated for 150 minutes on the basolateral surface of confluent and inverted T-84 monolayers separated by fluoroblock insert membranes. Chemotactic gradients of n-formyl methionyl leucyl phenylalanine (fMLP), eotaxin, and platelet aggregating factor (PAF) were used in variable concentrations. Changes in transepithelial electrical resistance (TEER) were compared with baseline values. RESULTS: Differentiated HL-60 eosinophils undergo migration in response to fMLP, PAF, and eotaxin. Migration is associated with a drop in TEER. CONCLUSION: In this model, HL-60-differentiated eosinophils migrate in response to stimulants chemotactic for human eosinophils. The transepithelial migration of eosinophils is associated with epithelial barrier dysfunction, which may contribute to the development of disease.