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ScienceWeek
MEDICAL BIOLOGY: ON FIBROMUSCULAR DYSPLASIA
The following points are made by D.P. Slovut and J.W. Olin (New Engl. J. Med. 2004 350:1862):
1) Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects the renal and internal carotid arteries but has been described in almost every arterial bed in the body (1-5). Although the disease was first described by Leadbetter and Burkland in 1938, the report by McCormack and coworkers two decades later of four cases of "fibromuscular hyperplasia" was the first accurate pathological description of this entity. The clinical presentation may vary from an asymptomatic condition to a multisystem disease that mimics necrotizing vasculitis, depending on the arterial segment involved, the degree of stenosis, and the type of fibromuscular dysplasia.
2) The pathological classification scheme for fibromuscular lesions of the renal arteries is based on the arterial layer --intima, media, or adventitia -- in which the lesion predominates.16 Macroaneurysms and dissections are complications of fibromuscular dysplasia and do not represent distinct histopathological categories.
3) Medial fibroplasia, which is characterized by its classic "string of beads" appearance, represents the most common dysplastic lesion.(4) Typically, the beading is larger than the normal caliber of the artery and is located in the middle-to-distal portion of the artery. Histologically, there is involvement of the media, whereas the intima, internal elastic lamina, and adventitia are preserved.(4) The lesion of perimedial fibroplasia is characterized by a homogeneous collar of elastic tissue at the junction of the media and the adventitia. The elastic elements of the media and intima appear normal. Perimedial fibroplasia is diagnosed when focal stenoses and, occasionally, multiple constrictions are observed, often with a robust collateral network. The "beads" are usually less numerous than in medial fibroplasia and are typically smaller in diameter than the normal caliber of the artery. Medial hyperplasia accounts for less than 1 percent of arterial stenoses and may be indistinguishable angiographically from intimal fibroplasia.
4) Although a variety of genetic, mechanical, and hormonal factors have been proposed, the cause of fibromuscular dysplasia remains unknown. Cigarette smoking and a history of hypertension are associated with an increased risk of this condition. No association has been found between fibromuscular dysplasia and previous use of oral contraceptives or abnormalities of endogenous sex hormones. Genetic factors may play a part in the development of fibromuscular dysplasia, since the disease is more common among the first-degree relatives of patients with fibromuscular dysplasia of the renal arteries and among persons with the angiotensin-converting-enzyme allele ACE-I.24
5) It is usually not difficult to differentiate atherosclerosis from fibromuscular dysplasia. Atherosclerosis generally occurs at the origin or proximal portion of the artery in older patients with typical cardiovascular risk factors. In contrast, fibromuscular dysplasia occurs in the middle or distal arterial segments in younger patients with few cardiovascular risk factors.
6) At times it may be difficult to distinguish fibromuscular dysplasia from vasculitis. Fibromuscular dysplasia is, by definition, a noninflammatory process and is therefore not associated with anemia, thrombocytopenia, or abnormalities of acute-phase reactants, except when it occurs during acute infarction. Large-vessel vasculitis may occur in the absence of changes in acute-phase reactants in up to 40 percent of cases.32 When histologic proof or markers of inflammation are unavailable, it may be difficult to distinguish these entities, because their angiographic appearance may be similar, especially if the intimal fibroplasia is of the multivessel type.
References (abridged):
1. Kojima A, Shindo S, Kubota K, et al. Successful surgical treatment of a patient with multiple visceral artery aneurysms due to fibromuscular dysplasia. Cardiovasc Surg 2002;10:157-160
2. Insall RL, Chamberlain J, Loose HW. Fibromuscular dysplasia of visceral arteries. Eur J Vasc Surg 1992;6:668-672
3. Luscher TF, Keller HM, Imhof HG, et al. Fibromuscular hyperplasia: extension of the disease and therapeutic outcome: results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia. Nephron 1986;44:109-114
4. Stanley JC, Gewertz BL, Bove EL, Sottiurai V, Fry WJ. Arterial fibrodysplasia: histopathologic character and current etiologic concepts. Arch Surg 1975;110:561-566
5. Cutts S, Grewal RS, Downing R. Bilateral brachial artery fibromuscular dysplasia. Eur J Vasc Endovasc Surg 2000;19:667-668
New Engl. J. Med. http://www.nejm.org
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Related Material:
BIOLOGY OF ATHEROSCLEROSIS
Notes by ScienceWeek:
"Arteriosclerosis" is a generic term for several diseases in which the arterial wall becomes thickened and loses elasticity, and "atherosclerosis" is a form of arteriosclerosis characterized by patchy thickening (atheroma) in the subintimal layer (i.e., immediately below the innermost layer) of medium and large arteries, the thickening capable of reducing or obstructing blood flow.
In this context, the term "plaque" refers to any patch or small differentiated area in or on arterial endothelium.
In general, the term "endothelium" refers to a layer of flat cells lining blood vessels, lymphatic vessels, the heart, etc. Atherosclerotic plaque consists of accumulated intracellular and extracellular lipids, smooth muscle cells, connective tissue, and *glycosaminoglycans.
Two main hypothesis have been proposed to explain the pathogenesis of atherosclerosis: a) the lipid hypothesis postulates that an elevation in plasma low-density-lipoprotein (LDL) cholesterol levels results in penetration of LDL into the arterial wall with a consequent series of cellular events leading to the formation of plaque; b) the chronic endothelial injury hypothesis postulates that endothelial injury by various mechanisms produces loss of endothelium and a consequent series of events (inflammatory response) involving blood cellular entities, the events leading to the formation of plaque. The current consensus is that these two hypotheses are probably interrelated.
The following points are made by Russell Ross (New England J. Med. 1999 340:115):
1) Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principle risk factors for atherosclerosis, the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall. However, the disease is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations, cardiovascular disease continues to be the principal cause of death in the US, Europe, and much of Asia. In fact, the lesions of atherosclerosis represent a series of highly specific cellular and molecular responses that can best be described, in aggregate, as an inflammatory disease.
2) The lesions of atherosclerosis occur principally in large and medium-sized elastic and muscular arteries and can lead to *ischemia of the heart, brain, or extremities, resulting in *infarction. They may be present throughout a person's lifetime. In fact, the earliest type of lesion, the so-called "*fatty streak", which is common in infants and young children, is a pure inflammatory lesion, consisting only of *monocyte-derived *macrophages and *T-lymphocytes. In persons with *hypercholesterolemia, the influx of these cells is preceded by the extracellular deposition of amorphous and membranous lipids. The author suggests that by asking questions about arterial inflammation, we may be able to gain insight into the process of atherogenesis.
3) The author proposes the following as possible causes of endothelial dysfunction (and a concomitant inflammatory response) leading to atherosclerosis: a) elevated and modified LDL; b) free radicals caused by cigarette smoking, *hypertension, and *diabetes mellitus; c) generic alterations; d) elevated plasma *homocysteine concentrations; e) infectious microorganisms such as *herpesviruses or *Chlamydia pneumoniae; e) combinations of these or other factors. The author suggests that regardless of the cause of endothelial dysfunction, atherosclerosis is a highly characteristic response of particular arteries.
4) The author concludes: "Atherosclerosis is clearly an inflammatory disease and does not result simply from the accumulation of lipids."
New Engl. J. Med. http://www.nejm.org
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Notes by ScienceWeek:
glycosaminoglycans: In general, any polysaccharide containing a substantial proportion of aminomonosaccharide residues.
inflammatory disease: In general, inflammation is a fundamental pathologic process consisting of a dynamic complex of cellular and chemical reactions occurring in affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by physical, chemical, or biological agents.
ischemia: In general, a sudden loss of blood supply to a tissue caused by blockage of a blood vessel.
infarction: (infarct) An area of necrosis caused by a sudden insufficiency of blood supply.
fatty streak: Consists of lipid-laden *monocytes and *macrophages (together, in a fatty streak, called "foam cells"), plus *T-lymphocytes. Later, these cell types are joined by various numbers of smooth muscle cells, the entire mass partially obstructing the lumen of the artery.
monocyte: The monocytes are the largest of the leukocytes (white blood cells). macrophages are amoeba-like leukocytes that are able to surround and digest foreign entities such as bacteria and protozoa.
macrophages: Amoeba-like leukocytes that are able to surround and digest foreign entities such as bacteria and protozoa.
T-lymphocytes: (T-cells) Lymphocytes (lymph cells, lympho-leukocytes) are a type of leukocyte (white blood cell) involved in the immune response. There are two classes of such lymphocytes: 1) the B-cells, which after a cascade of immune system events involving a specific antigen change into proliferating specific antibody producing plasma cells; 2) the T-cells, one subclass of which (cytotoxic T-cells) interacts directly with foreign invaders such as bacteria and viruses, while the other subclass of T-cells (helper T-cells) is involved in the proliferation of antibody-specific B-cells.
hypercholesterolemia: The presence of an abnormally large amount of cholesterol in the cells and plasma of circulating blood.
hypertension: In general, high blood pressure.
diabetes mellitus: Diabetes mellitus is a metabolic disease in which carbohydrate utilization is reduced and that of lipid and protein enhanced. The disease is caused by an absolute or relative deficiency of insulin, and there are many forms of the disease recognized. The term "diabetes" can refer to either diabetes mellitus or diabetes insipidus, both diseases characterized by chronic excretion of large amounts of urine (polyuria). But when the term "diabetes" is used alone, what is usually meant is diabetes mellitus.
homocysteine: An intermediate in the biosynthesis of cysteine, recently considered to be of significance in cardiovascular disease.
herpesviruses: The herpesviruses are a class of viruses producing the complex of herpes diseases. The outstanding property of herpesviruses is their ability to establish lifelong persistent infections in their hosts and to undergo periodic reactivation. They are large viruses, 150 to 200 nanometers in diameter, with a core of double-stranded DNA.
Chlamydia pneumoniae: A common species of pathogenic gram-negative bacteria. Worldwide, 30 to 50 percent of people have antibodies to this pathogen.
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