Preservation and structural adaptation of endothelium over experimental foam cell lesions. Quantitative ultrastructural study.

Self Cite

592

242

The compositions of lesion types that precede and that may initiate the development of advanced atherosclerotic lesions are described and the possible mechanisms of their development are reviewed. While advanced lesions involve disorganization of the intima and deformity of the artery, such changes are absent or minimal in their precursors. Advanced lesions are either overtly clinical or they predispose to the complications that cause ischemic episodes; precursors are silent and do not lead directly to complications. The precursors are arranged in a temporal sequence of three characteristic lesion types. Types I and II are generally the only lesion types found in children, although they may also occur in adults. Type I lesions represent the very initial changes and are I n this report we characterize lesions that precede and may initiate the development of advanced atherosclerotic lesions. Advanced lesions are defined as those in which an accumulation of lipid in the intima is associated with intimal disorganization and thickening, deformity of the arterial wall, and often with complications such as fissure, hematoma, and thrombosis. Advanced lesions may produce symptoms, but the lesions that precede them are clinically silent.This report is the second in a series of three. The first 1 provided a definition of the arterial intima and its atherosclerosis-prone regions. The third report will describe the different types of advanced atherosclerotic lesions and will provide a histological classification of all human atherosclerotic lesion types. The precursors of advanced lesions are divided into three morphologically characteristic types. Both type I and II lesions represent small lipid deposits in the arterial intima, and type II includes those lesions generally referred to as fatty streaks. Type III represents the stage that links type II to advanced lesions. The term "early lesions" is sometimes used for type I and II lesions. "Early" implies that these lesions are followed by "later" (advanced) lesions. It also implies that they are found early in life. Neither implication is necessarily "A Definition of Initial, Fatty Streak, and Intermediate Lesions of Atherosclerosis" was approved by the American Heart Association SAC/Steering Committee on October 20, 1992.Requests for reprints should be sent to the Office of Scientific Affairs, American Heart Association, 7272 Greenville Ave, Dallas, TX 75231-4596. true, although types I and II are generally the only lesions present in children, and there is evidence that certain type II lesions are prone to proceed to type III and more advanced lesions.The distinctions that separate individual lesion types are based on consistent morphological characteristics, which indicate that each type may stabilize temporarily or permanently and that progression to the next type may require an additional stimulus. The morphological features of each type of lesion and the time at which each tends to occur and predominate in the course of a human life are strong presumptive evid...

Section: Endothelial Cellsmentioning

confidence: 99%

Section: Endothelial Cellsmentioning

confidence: 99%

A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

Stary

Chandler

Glagov

et al. 1994

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592

242

“…15 The carotid arteries including the common carotid artery and its internal and external carotid branches were then filled with a mixture of barium sulfate in a molten gelatin solution. When the gelatin solidified, angiograms were made.…”

Section: Specimen Preparation and Plaque Quantificationmentioning

confidence: 99%

Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate.

Beere

Glagov

Zarins

1992

Self Cite

115

We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino-atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148±11 to 103±20 beats/min, p<0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136±22 beats/min), animals were separated into a low-heart-rate (LHR) group (111+16 beats/min, n=12) and a high-heart-rate (HHR) group (150±16 beats/min, n=5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross-sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01 ±1.19 compared with 0.76±0.42 mm 2 for lesion area [p<0.02] and 30.7±4.4% compared with 15.2±7.3% for stenosis [p<0.002]). When the single section with the largest lesion at each bifurcation was considered, all in the HHR group but only half of those in the LHR group had greater than 25% stenosis (p<0.03). Artery size, as indicated by the area encompassed by the internal elastic lamina, increased with plaque area. For the sections with little or no plaque immediately proximal or distal to the bifurcation, the internal elastic lamina area was similar for both groups. We conclude that axial and circumferential plaque distribution about the cynomolgus monkey carotid bifurcation is similar to that observed in humans, that plaque formation induced compensatory artery enlargement, and that plaque progression was retarded by lowered heart rate. The findings suggest that the conditions that determine plaque location and adaptive modeling in human atherogenesis also prevail in the cynomolgus monkey. (Arteriosclerosis and Thrombosis 1992;12:1245-1253 KEY WORDS • experimental atherosclerosis • carotid bifurcation • compensatory enlargement • heart rate • plaque localization A the human carotid bifurcation, plaques form predominantly in the proximal internal carotid segment, opposite the flow divider, where wall shear stress is low and flow separation and vortex formation occur.1 In addition, wall shear stress in this region oscillates in both magnitude and direction during the cardiac cycle.2 At the relatively spared flow-divider side, wall shear stress is high and re...

“…2 - 3 The importance of mild injury as an atherogenic factor in a normal or even a mildly hyperlipemic setting remains to be defined.…”

Section: Increased Endothelial Replication In Diabetic Vessels Was Shmentioning

confidence: 99%

Intimal alterations in rabbit aortas during the first 6 months of alloxan-induced diabetes.

Hadcock

Richardson

Winocour

et al. 1991

Diabetes mellihis is a major risk factor for atherosclerosis. Since endothelial alteration is probably associated with the development of atherosclerosis, we questioned whether morphological evidence of endothelial injury could be observed during the first 6 months of diabetes induced by a single intravenous injection of alloxan in normally fed rabbits compared with age-matched controls. Diabetes (plasma glucose >16 mM) was established by 5 days after alloxan injection. Endothelial alterations consistent with injury, including adhesion of white blood cells, platelets, and fibrin-like material to the endothelial surface, were seen in diabetic rabbit aortas by 2 weeks. These alterations became more severe during the next 6 months. Increased endothelial replication in diabetic vessels was shown by the uptake of tritium-labeled thymidine at 2 weeks and at 3 and 6 months. Hyperplasia of intimal smooth muscle cells progressed during 3 months after treatment About one third of the diabetic rabbits also showed an elevated plasma cholesterol level, which correlated with increased intimal proliferation but not with endothelial injury or replication. The onset of alloxan-induced diabetes in rabbits is associated with nondenuding endothelial injury and subsequent intimal hypertrophy, changes that are consistent with atherogenesis. (Arteriosclerosis and Thrombosis 1991;ll:517-529)