Complicated Atherosclerotic Plaques Research Articles

Quantitative angiographic morphology of the coronary artery lesions at risk of thrombotic occlusion.

Coronary angiography in acute myocardial infarction has revealed complicated atherosclerotic plaque and a high rate of thrombotic occlusion. However, the characteristics of lesions at high risk of subsequent occlusion are not well known. In the present study, the qualitative and quantitative angiographic features of 38 coronary artery lesions that occluded within 3 years to cause an acute myocardial infarction were compared with 64 control segments from the same patients that did not occlude. Compared with control lesions, the lesions that occluded were more likely to have a division branch originating within the stenosis (76% versus 52%, p less than 0.05). The percent lumen diameter reduction was more severe (47.5 +/- 17.8% versus 41 +/- 12.5%, p less than 0.05) and the inflow (21 +/- 10 degrees versus 16 +/- 7 degrees, p less than 0.05) and outflow (20 +/- 10 degrees versus 16 +/- 8 degrees, p less than 0.05) angles of the stenosis were steeper. Time to myocardial infarction after the angiogram interacted with the importance of these features (p less than 0.02). Thus, paired analysis of the lesions that occluded within 3 months and of the most severe control lesion from each patient showed percent lumen diameter reduction of 62.1 +/- 11.5% and 46.4 +/- 11.4%, respectively (p less than 0.001). The length of the stenosis, its asymmetry, and the irregularity of the contours did not help differentiate occlusive from control segments. Coronary artery lesions at high risk of thrombotic occlusion share common characteristics that favor higher shear stress and flow separation.

Angiogenic activity of the atherosclerotic carotid artery plaque

Neovascularization is observed in complicated atherosclerotic plaques associated with cellular proliferation, plaque hemorrhage, and thrombosis. The angiogenic activity of 278 plaque fragments was tested; the fragments were taken from 12 patients with cerebral ischemia who underwent carotid endarterectomy. Angiogenesis, determined by the sustained ingrowth of new vessels in the rabbit cornea, was induced in 125 (45%) of these fragments. By contrast, angiogenesis was found in only two (2.4%) of 80 control tissues (p less than 0.001): in none of 22 samples of boiled atherosclerotic plaque; in two of 26 samples of normal rabbit carotid artery; and in none of 32 samples of nonatherosclerotic human uterine artery. Histological evaluation revealed that the cellular zones (composed mainly of smooth-muscle cells) were highly angiogenic, with 97 (76%) of 127 samples showing angiogenesis compared with 23 (17%) of 132 acellular fragments that consisted of amorphic, necrotic, calcific, lipid-laden material (p less than 0.001). These results indicate that angiogenesis in vivo is a function of the cellular component of the advanced atherosclerotic plaque, and is not expressed in the normal, stable arterial wall. The fragile new vessels could promote the growth of the plaque or be a source of hemorrhages, microinfarcts, and plaque fissures that convert a stable, silent lesion to an expanding, ulcerated, thrombotic, symptomatic plaque.

Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells.

Proliferation of vascular smooth muscle cells (SMC) contributes to formation of the complicated human atherosclerotic plaque. These lesions also contain macrophages, known to secrete SMC mitogens, and T lymphocytes. Many of the SMC in the lesions express class II major histocompatibility antigens, an indication that activated T cells secrete immune IFN-gamma locally in the plaque. We therefore studied the effect of IFN-gamma on the proliferation of cultured SMC derived from adult human blood vessels. IFN-gamma (1,000 U/ml) reduced [3H]thymidine (TdR) incorporation into DNA by SMC stimulated with the well-defined mitogens IL 1 (from 15.3 +/- 0.7 to 6.2 +/- 0.7 dpm X 10(-3)/24 h) or platelet-derived growth factor (PDGF) (from 18.5 +/- 1.0 to 7.3 +/- 0.7 dpm X 10(-3)/24 h). Kinetic and nuclear labeling studies indicated that this effect of IFN-gamma was not due to altered thymidine transport or specific radioactivity of TdR in the cell. In longer term experiments (4-16 d) IFN-gamma prevented net DNA accumulation by SMC cultures stimulated by PDGF. IFN-gamma also delayed (from 30 to 60 min) the time to peak level of c-fos RNA in IL 1-treated SMC. It is unlikely that cytotoxicity caused these effects of IFN-gamma, as the inhibition of growth was reversible and we detected no cell death in SMC cultures exposed to this cytokine. Activation of 2'-5' oligoadenylate synthetase gene expression may mediate certain antiproliferative and antiviral effects of interferons. Both IFN-gamma and type I IFNs (IFN-alpha or IFN-beta) induced 2'-5' oligoadenylate synthetase mRNA and enzyme activity in SMC cultures, but with concentration dependence and time course that may not account for all of IFN-gamma's cytostatic effect on SMC. The accumulation of SMC in human atherosclerotic lesions is a long-term process that must involve altered balance between growth stimulatory and inhibitory factors. The cytostatic effect of IFN-gamma on human SMC demonstrated here may influence this balance during human atherogenesis, because T cells present in the complicated atherosclerotic plaque likely produce this cytokine.

FATAL ATHEROSCLEROSIS DEVELOPED IN LESS THAN 4 YEARS IN AORTOCORONAR VEIN GRAFT IN A HYPERLIPIDEMIC PATIENT

It is generally believed that it takes decades to develop a complicated atherosclerotic plaque. This view is challenged by the present case describing a hyperlipidemic patient who died of vein graft atherosclerosis less than 4 years after otherwise successful coronary bypass surgery. Although the atherogenesis may be accelerated in autogenous coronary vein grafts compared with native coronary arteries, the present case illustrates that complicated atherosclerosis may develop in the course of only a few years if appropriate conditions prevail.

Regional aortic differences in atherosclerosis-susceptibility: changes in prostaglandin biosynthesis and cholesterol accumulation in response to desoxycorticosterone (DOCA)-salt induced hypertension.

In spontaneously atherosclerosis-susceptible White Carneau pigeons, intimal cushions that appear at birth near the coeliac branch of aorta do not progress into atherosclerotic lesions. However, the area across from the intimal cushion (so called 'lesion area') a) accumulates cholesteryl esters b) synthesizes more PGE2 and c) eventually develops into complicated atherosclerotic plaques. When DOCA-salt hypertension is induced in the pigeons, the 'initimal cushion' area displays a) accumulation of increasing amounts of cholesteryl esters and b) increase in the synthesis of all prostaglandins (particularly PGE2) from C14-arachidonic acid and c) approaches similarity to the 'lesion area' in the magnitude of these changes. These results suggest that under the influence of a risk factor, the 'intimal cushion' can acquire biochemical properties of the atherogenic areas of the aorta.

Aortic size and aortic calcification: A necropsy study

Measurements of aortic length and circumference in 336 post-mortem specimens confirm earlier, neglected observations on the progressive increase in aortic size which occurs with advancing years. The increase is not related to atherosclerosis, or to hypertension and seems to be part of a true ageing process. The value of measurement of aortic size in body age determination merits exploration by forensic pathologists. Aortic calcification is found in raised and complicated atherosclerotic plaques and its prevalence and severity closely follows the accepted pattern of plaque severity, occurring earlier and more severely in men, in the abdominal aorta and in patients with overt vascular disease in other territories such as patients with cardiac infarcts. No association was found between the amount of calcification and the presence of hypertension, diabetes or neoplasia.