Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Left ventricular hypertrophy may be considered the result of an interaction of a myriad of factors, including hemodynamic overload; age, race, and gender of the patient; the stage of hypertensive disease; and other coexisting diseases. This concept is similar to the multifactorial "mosaic of hypertension" described by Page. In addition, the increased left ventricular mass in hypertension may reflect the disposition of collagen tissue and the participation of a myriad of myocytic growth factors, as well as drug therapy. The resultant left ventricular hypertrophy confers increased cardiovascular risk that is independent of the height of arterial pressure. The mechanisms that account for that risk are not yet well understood but include reduced adaptive myocardial reserve, enhanced predisposition to cardiac dysrhythmias and cardiac failure, accelerated atherosclerosis, and reduced (absolute and relative) coronary flow and flow reserve, as well as other possibilities. At present much work is directed to the demonstration of pharmacological reversal of hypertrophy. However, even with that demonstration of reduced cardiac mass with therapy, it will be necessary to show improved risk at the reduced mass that is independent of the reduction of arterial pressure as well as of the effects of those drugs on cardiac rhythm, flow, metabolism, and direct effects on the cardiac myocyte itself.
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PMID:The heart in hypertension: a 1991 overview. 183 56

Most ischemic heart disease in associated with severe coronary atherosclerosis. A small subset of patients, however, had angina pectoris despite angiographically normal coronary arteries and absence of inducible coronary spasm. Coronary microcirculation (i.e. arteries too small to be visualized by current angiographic techniques) has been identified as the weak point of these patients. Small coronary vessel involvement may be due to organic conditions (such as diabetes, vasculitis, systemic collagen-vascular diseases, infectious processes) that act through coronary thrombosis or embolism and related alteration in coronary vasomotion; alternatively, the vascular abnormality appears to be entirely functional (no ultrastructural myocardial changes) such as the case of hypertension, hypertrophic cardiomyopathy and syndrome X. Whatever the cause(s) and mechanism(s) of the small coronary artery involvement, this leads to myocardial ischemia and to the related complications as in classic atherosclerotic heart disease. Syndrome X is characterized by effort-induced angina pectoris, ST-segment changes during exercise testing, negative ergonovine test and reduced coronary reserve. A pre-arteriolar hypersensitivity to vasoconstrictor influences (elicited by cold pressor test or ergonovine) and a reduced vasodilator capacity (unmasked by metabolic and pharmacological studies) have been proposed as potential pathogenetic substrate. This dynamic alteration in vasomotion would answer for both symptoms and signs of myocardial ischemia, that, however, appear to be contemporarily elicitable in a minority of patients. Treatment with beta-blockers and calcium-antagonists has been found to be effective. The long-term follow-up shows favorable outcome with a high survival rate and a low incidence of cardiovascular events.
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PMID:[Angina due to microvascular pathology]. 184 63

Atherosclerosis of the infrarenal aorta results in distinct clinical entities--aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA). Although loss of collagen has been implicated in AAA, collagen accumulation plays a role in AOD. In vivo collagen-gene expression can be assessed using complementary DNA for collagen types I and III alpha-chains. The purpose of this study is to compare total collagen (type I + III) and collagen types I and III messenger RNA in AAA, AOD and normal aorta. Specimens were collected from the infrarenal aorta during operation for AOD (n = 7), AAA (n = 7), autopsy, or organ procurement (normal; n = 7). Northern transfer analysis of total RNA was used to compare mRNA levels for type I and III collagen. After preliminary extraction, specimens were hydrolyzed for hydroxyproline analysis used to calculate total collagen (type I + III). Relative levels of type I (pro-a1[1]) mRNA were greater in both AOD (0.77 +/- 0.35) and AAA tissue (0.94 +/- 0.24; p = 0.6) than in normal aorta (0.02 +/- 0.03). Type III (pro-a1[III]) mRNA levels were also greater in AOD (2.52 +/- 0.19; p = 0.09) and AAA tissue (3.15 +/- 1.3) than in normals (0.97 +/- 0.47). Total collagen concentration was increased in AOD (45.6% +/- 3.1% dry weight; p less than 0.05) but not AAA tissue (27.8% +/- 4%) when compared to normal aorta (34.7% +/- 2.3%). Collagen type I and III gene expression is greater in older, diseased aorta, yet collagen accumulated only in AOD. This implies a similar synthetic response in both AOD and AAA. Thus, proteolytic degradation in AAA appears to determine collagen content and possibly the clinical course of the atherosclerotic process.
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PMID:Aneurysm or occlusive disease--factors determining the clinical course of atherosclerosis of the infrarenal aorta. 185 45

Results show that diabetes, which is a major risk factor for arterio-atherosclerosis, mimicks an accelerated aging, at least as far as the thickening of basement membranes and fibronectin and collagen biosynthesis are concerned. A similar sequence of events could be demonstrated in human atherosclerotic plaque formation. In conclusion, we could demonstrate a disregulation of extracellular matrix components biosynthesis (type-III collagen and fibronectin) in diabetes and atherosclerosis.
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PMID:Modifications of the biosynthesis of type-I and type-III collagens and fibronectin during diabetes and atherosclerosis. 187 89

In this study, the fluorescent morphological structures in normal coronary artery, normal aorta, and atherosclerotic aorta were histochemically identified and spectroscopically characterized in situ using ultraviolet-excited microspectrofluorimetry. Excitation wavelengths of 290 nm and 310/312 nm were employed to observe two distinct fluorescence bands, with peak emission wavelengths near 335 nm and 380 nm, respectively. Emission of the short wavelength 335 nm band, previously assigned to tryptophan residues in tryptophan-containing proteins, was observed from all the morphological structures in the vessel walls and was isolated in groups of smooth muscle cells in aorta and coronary artery media. The long wavelength 380 nm band was assigned to distinct fluorophores associated with the structural proteins collagen and elastin and was observed in collagen fibers and elastic fibers, respectively. The corresponding morphological structures in normal aorta, normal coronary artery, and atherosclerotic aorta exhibited similar fluorescence lineshapes. In atherosclerotic plaque, a distinct fluorescence band, peaking near 370 nm, was observed in the emission from both ceroid granules and necrotic core. Using a simple, quantitative model, differing contributions of collagen, elastin, and tryptophan-containing protein fluorescence were shown to account for over 95% of the emission from the intima, media, and adventitia layers of non-necrotic aorta and coronary artery.
Atherosclerosis 1991 May
PMID:Characterization of the fluorescent morphological structures in human arterial wall using ultraviolet-excited microspectrofluorimetry. 187 5

Hypercholesterolemia (mean plasma cholesterol: 15 mM) was induced in rabbits by the feeding of a chow diet enriched with a low amount (0.25%, w/w) of cholesterol only. Platelet size and protein content decreased significantly, but the whole blood platelet count did not change. The platelets became enriched in cholesterol, as indicated by a significant increase in the cholesterol:phospholipid molar (C/P) ratio. Specific responses of washed platelets stimulated with various agonists were studied to determine the effects of hypercholesterolemia on the various pathways of platelet aggregation in the absence of plasma components. In platelets from hypercholesterolemic rabbits compared with controls: aggregation induced by ADP was not altered; collagen-induced responses (aggregation, secretion of [14C]serotonin from prelabelled platelets, thromboxane A2 (TXA2) formation, mobilization of [3H]arachidonate from prelabelled platelets) were enhanced; with aspirin-treated platelets, aggregation induced by the TXA2 mimetic U46619 was enhanced: and thrombin-induced responses of both untreated platelets (aggregation, secretion of granule contents, TXA2 formation) and aspirin-treated platelets (aggregation) were enhanced. Thus, platelets from cholesterol-fed rabbits not only form more TXA2, but they aggregate more extensively when stimulated by its mimetic. In addition, it has not been previously recognized that these platelets are also hypersensitive to thrombin-induced aggregation that is independent of TXA2.
Atherosclerosis 1991 May
PMID:Platelet hypersensitivity in cholesterol-fed rabbits: enhancement of thromboxane A2-dependent and thrombin-induced, thromboxane A2-independent platelet responses. 187 12

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.
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PMID:Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. 189 66

Enhanced macrophage cholesterol accumulation is associated with foam cell formation in the atherosclerotic lesion. Since platelet activation plays an important role in atherogenesis, we questioned whether products released from activated platelets could affect macrophage cholesterol metabolism. The addition of platelet-conditioned medium (PCM, obtained from collagen activated platelets) to a J-774 macrophage cell line, enhanced cellular cholesteryl ester content by 32%. The cholesterol esterification rate was also increased by 29%. Pre-loading the macrophages with cholesterol by incubation with acetyl-LDL, resulted in a further elevation of 48% in PCM-mediated cholesterol esterification. Possible mechanisms for the enhanced cholesterol esterification by J-774 macrophages following incubation with PCM include increased cholesterol influx and/or decreased cholesterol efflux (These cells were recently shown not to synthesize cholesterol). However, both increased uptake of PCM cholesterol by the macrophages as well as increased cellular cholesterol efflux (by 22%) were noted. The enhancement of cholesterol esterification by PCM was competitively inhibited by fucoidin and polyinosinic acid, implicating PCM binding to the scavenger receptor. This was further evidenced by the observations that apolipoprotein E which reduces cellular uptake via the scavenger receptor but not via the LDL receptor, also inhibited the effect of PCM, whereas IgG C-7, the LDL receptor antibody, did not alter the effect of PCM. Lysosomal involvement in the cellular processing of PCM was observed since PCM activity was inhibited by the lysosomal inhibitor, chloroquine. Partial purification of PCM by gel filtration revealed that the cholesterol component was associated with both phospholipids and proteins in a lipoprotein-like particle. Delipidation of PCM resulted in its inactivation but both heat treatment and tryptic digestion of PCM, revealed that the protein (and not only the cholesterol) component was also essential for the effect of PCM on cellular cholesterol esterification. Furthermore, PCM prepared from platelets of a patient with Gray Platelet Syndrome that lack platelet alfa granules (which contain platelet specific proteins), failed to enhance cholesterol esterification. These results demonstrate that lipoprotein-like particles released during platelet activation can interact with the macrophage scavenger receptor thus leading to enhanced cellular cholesterol accumulation.
Atherosclerosis 1991 Jun
PMID:Platelet secreted lipoprotein-like particle is taken up by the macrophage scavenger receptor and enhances cellular cholesterol accumulation. 189 83

We have shown that normal coronary arteries and noncalcified and calcified atherosclerotic plaque can be differentiated on the basis of the 476 nm excited fluorescence spectra, providing the basis of a spectroscopic guidance system for coronary artery laser angiosurgery. This discrimination is based on extraction of parameters from tissue fluorescence spectra, which are proportional to the tissue concentrations of structural proteins (collagen and elastin) and ceroid via a model of tissue fluorescence. We use these parameters to calculate the likelihood that an area of interest in a coronary artery is normal, noncalcified, or calcified plaque. This method of diagnosing atherosclerosis provides information about the histochemical composition of atherosclerotic lesions and is thus fundamentally different from the diagnostic methods currently used. It may ultimately have bearing on a number of pertinent clinical problems. We have discussed applications to studying initiating factors in formation and progression of plaque, healing after interventional treatments, and the likelihood of restenosis after PTCA.
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PMID:476 nm excited laser-induced fluorescence spectroscopy of human coronary arteries: applications in cardiology. 192 64

Epidemiological surveys show the clear association of hypertension with an increased risk of developing ischaemic heart disease. One method of quantifying atherosclerosis is to measure, at necropsy, the percentage of the intimal surface of the coronary arteries or aorta which is occupied by raised plaques. When this is done in a large number of subjects the amount of intimal involvement in any particular geographical population correlates directly with the frequency of ischaemic heart disease. In all these populations, whether at a high risk or low risk of developing ischaemic heart disease, hypertensive subjects have a greater intimal involvement by plaques than normotensive subjects. Thus, the increased risk in hypertension is, in part, mediated by possession of more plaques. Plaque growth is due to the accumulation of lipid from the plasma, the ingress of monocytes with their conversion to lipid filled foam cells and the formation of collagen by smooth muscle cells. Hypertension may act by altering endothelial function to potentiate all these processes. Mechanical stress on endothelial cells will evoke the formation of growth factors for smooth muscle cells. Plaque growth in man is also episodic due to the formation of thrombi; a proportion of these episodes are symptomatic producing acute myocardial ischaemia but the majority are silent leading to sudden plaque expansion. Thrombi over plaques are either due to endothelial denudation injury or more commonly due to the tearing of the cap of a plaque leading to deep intimal injury. Necropsy surveys of control populations show that subjects with hypertension have a greater frequency of recent plaque tears compared with normotensive subjects.
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PMID:Hypertension and atherosclerotic (ischaemic) heart disease. 194 81


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