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

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
 ...
PMID:Diabetes-induced abnormalities in the myocardium. 293 41

We have raised specific antibodies against the protein component of baboon lipoprotein (a) (Lp(a]. Apolipoprotein (apo) Lp(a) is a very large protein which separates into two distinct proteins, apo B and apo (a), when 2-mercaptoethanol is included during sample treatment for sodium dodecyl sulfate-electrophoresis. The antibodies were specific for baboon apo (a) and apo B. The presence of the two distinct antigens in the lipoprotein permitted the development of an enzyme-linked immunosorbent assay that was specific for Lp(a) particles in serum. The assay could detect less than 1 ng of Lp(a) protein per well and was useful in the range of 1-9 ng. The assay was specific for Lp(a) and did not respond to other lipoproteins, such as low density lipoprotein. Lp(a) could be accurately quantitated in serum frozen at -80 degrees C in plastic tubing segments. Using the Lp(a) assay, the mean serum level of 80 unrelated baboons was 4.7 mg/dl, with the distribution skewed toward the lower levels. These data further support the value of the baboon as a model of the atherogenic lipoprotein Lp(a).
Atherosclerosis 1988 Sep
PMID:Immunochemical characterization and quantitation of lipoprotein (a) in baboons. Development of an assay depending on two antigenically distinct proteins. 297 92

Fourteen male patients with mild essential hypertension were put on a mackerel and herring diet within a prescribed isocaloric regimen in a cross-over design for 2 weeks. After mackerel diet eicosapentaenoic acid (EPA-C20:5, n-3) appeared more in cholesterol esters (1.7-11.0%), whereas docosahexaenoic acid (DHA-C22:6, n-3) was predominantly incorporated into serum triglycerides (1.0-8.3%). After herring diet, which contained half as much EPA and DHA, their increase was of minor degree. After mackerel diet serum triglycerides, total cholesterol, LDL cholesterol and lecithin cholesterol acyl transferase (LCAT) activity were significantly decreased (by 28%, 9%, 14% and 14%, respectively), returning to the initial levels 3 months later. On the contrary, HDL cholesterol appeared significantly increased (by 12%). After herring diet the differences were not significant. Serum sodium was significantly lower (by 2%) at the end of the mackerel diet as compared to the initial values. On the other hand, uric acid in serum appeared transiently increased (by 24%) at the end of both dietary periods. A significant decrease (by 8%) in casual systolic blood pressure, measured in recumbent position, could be observed only at the end of the mackerel period. Moreover, the level of systolic and diastolic blood pressure before and during a standardized psychophysiological stress test was significantly lower after mackerel diet. Nevertheless, the increments after stress were similar. Plasma renin activity was increased (by 64%) after mackerel diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1985 Aug
PMID:Blood pressure- and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension. 300 Mar 95

The effect of epinephrine on 125I-low density lipoprotein (LDL) uptake and cholesterol metabolism was investigated after a 24 hours pretreatment of cultured human fibroblasts. Epinephrine decreased LDL uptake (binding + internalization) and degradation in a dose-dependent manner. Cholesterol synthesis from 14C sodium acetate and cholesterol esterification measured by 14C oleic acid incorporation into cholesteryl esters were also decreased. These results are in agreement with the general view that epinephrine increases cyclic AMP intracellular level, as it was previously demonstrated that dibutyryl cyclic AMP or isoproterenol treatment of cultured fibroblasts had similar effect on these pathways. The decrease in LDL processing induced by epinephrine could be involved in the worsening effect of epinephrine on atherosclerosis.
 ...
PMID:Epinephrine decreases low density lipoprotein processing and lipid synthesis in cultured human fibroblasts. 300 79

Functional and biochemical alterations of platelets in patients suffering from atherosclerosis were studied in our laboratory. One of the most striking alterations observed is in the platelet active glucose transport system. The Na+/K+ gradient dependent active transport system of glucose is found to be absent in the platelets of atherosclerotics. The platelet glucose transport kinetics in these subjects give unsaturable and linear kinetics. Furthermore, the specific glucose binding protein activity detected in the incubation fluid after cold osmotic shock to the platelets of normal subjects is found to be absent in the platelets of atherosclerotics. The platelet active glucose transport system is normal in juvenile onset diabetics, whereas it is impaired in maturity onset diabetics with clinical manifest atherosclerosis. The release inducers like ADP, adrenalin and collagen exert no effect on the platelet active glucose transport system. The specific glucose-binding protein is an unreleasable protein in the platelets of normal subjects. Hence, the absence of active glucose transport system in atherosclerotics is not due to the activated platelets in circulation.
 ...
PMID:Alteration of platelet glucose transport system in atherosclerosis. 301 May 81

Isolation of non-esterified [14C]cholesterol bound to albumin from rat serum, 8 days after i.p. injection of [14C]cholesterol, was achieved by affinity chromatography, using Cibacron blue F3GA bound to Sepharose 4B and by Sephadex G-150 column chromatography. Both methods permit isolation of large quantities of cholesterol-loaded albumin, free of globulins and lipoproteins. The isolated albumin-cholesterol fraction was estimated to be 4.6 mg/100 ml serum, which represents approx. the 24% of the non-esterified cholesterol present in the rat serum. Albumin-cholesterol, cholesterol glucoside, cholesterol hemisuccinate and hydroxylated derivatives of cholesterol produced a biphasic curve of changes in synaptosomal plasma membranes (SPM)-bound (Na+ + K+)-stimulated ATPase activity. Low concentrations of the ligand progressively increased the enzyme activity, while increasing the ligand concentration above that which maximally stimulated the enzyme activity, produced a progressive inhibition. Lipoproteins did not have any effect on the enzyme activity. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene-labeled SPM, increased in albumin-cholesterol derivatives-treated SPM, which is consistent with a general decrease in membrane bilayer fluidity. The results provide evidence that the 'albumin-cholesterol' fraction of the serum may directly affect the cell membrane-bound enzyme activity.
Atherosclerosis 1986 Jul
PMID:Evidence for the existence of non-esterified cholesterol carried by albumin in rat serum. 301 57

Arterial hypertension (AH) is an excessive elevation of the arterial blood pressure (ABP) in the systemic circulation. It is, however, arbitrary to define a limit between normal and pathological ABP, since the ABP varies in a continuous fashion with the population. Occasional measurement of the blood pressure by sphygmomanometer is rather inaccurate but still remains the method of reference. A more precise determination of the ABP is possible by using the stress blood pressure profile and ambulatory measurement which are prognostically far superior to occasional measurement. AH is not a disease but a risk factor--quantitative and independent of the cardio-vascular system because it contributes to atherosclerosis and regional ischemic processes. The genesis of the so called essential AH still remains unclear, but it is getting better known: from a genetic factor of predisposition, the respective roles of the salt and the kidney as a filter are determining, along with the more or less appropriate action of hormonal factors of the sodium excretion. This is combined with the complex and synergistic action of potent vasopressor mechanisms such as the sympathetic nervous system and the renin-angiotensin systems--circulating as well as in the tissues. AH presents haemodynamic abnormalities, which vary according to age, and among which the elevation of systemic vascular resistances is most characteristic. This is combined with a lack of compliance of the large arterial vessels, and secondarily, a hypertrophy, partially adaptive, of the entire cardiovascular system. This includes left ventricular hypertrophy which has harmful effects on intracardiac and coronary haemodynamics, resulting in an increased mortality. It is therefore necessary that the treatment, not only decrease the blood pressure, but also take into account the regional vascular outputs while respecting and improving the renal, cerebral and coronary circulations with general improvement of the vascular compliance. The treatment must also result in an early and lasting decrease of the myocardial hypertrophy. This is why the new anti-hypertensive treatments (conversion enzyme inhibitors and calcium inhibitors) represent a desirable therapeutic alternative to the classical treatment. Their prescription follows a few general rules, but must, however, remain very personalized with evaluation of the results at two levels: individual control of the ABP and mass benefit in terms of decreased cardiovascular morbidity and mortality.
 ...
PMID:[Essential arterial hypertension. From notion to treatment]. 306 94

Data from several epidemiologic studies have suggested that the prevalence of hypertension in patients with diabetes mellitus is approximately 1.5-2.0 times greater than in an appropriately matched nondiabetic population. In patients with insulin-dependent diabetes mellitus (IDDM), hypertension is generally not present at the time of diagnosis. As renal insufficiency develops, blood pressure rises and may exacerbate the progression to end-stage renal failure. In non-insulin-dependent diabetes mellitus (NIDDM), many patients are hypertensive at the time of diagnosis. The incidence of hypertension in NIDDM is related to the degree of obesity, advanced age, and extensive atherosclerosis that is typically present, and it probably includes many patients with essential hypertension. Several other pathophysiologic mechanisms also contribute to the genesis and maintenance of hypertension in the patient with diabetes. Hyperglycemia and increases in total-body exchangeable sodium may lead to extracellular fluid accumulation and expansion of the plasma volume. In some patients, alterations in the function of the renin-angiotensin-aldosterone system and vascular sensitivity to vasoactive hormones may also play a role. It has recently been suggested that hyperinsulinemia and insulin resistance may also contribute to the maintenance of an elevated blood pressure because insulin is known to promote sodium retention and enhance sympathetic nervous system activity. The evidence for these hypotheses and their respective contributions to the etiology of hypertension in IDDM and NIDDM are discussed.
 ...
PMID:Etiology and prevalence of hypertension in diabetic patients. 307 72

Exposure of rabbits for 12 weeks to 300 ppm carbon disulfide (CS2) for 6 h/day, 5 days/week, or to 25 mg/day of thiourea or 2% cholesterol in the diet, or to any combination thereof caused a significant reduction in the concentration of serum thyroxine (T4). The reduction of the concentration of serum T4 in rabbits by the treatments was completely offset by the inclusion of 0.1 mg/day of sodium levothyroxine in the diet. Ingestion of feed containing 2% cholesterol significantly increased the degree of atherosclerosis present in the aortic arch and significantly increased the oil red O positive lipid present in the heart and the aorta, with the aortic arch being the most severely affected. The response of the aorta and the heart to the 2% cholesterol diet was not significantly modified by concurrent exposure to CS2 by inhalation or by treatment with thiourea, a metabolite of CS2. We found no evidence that the development of cardiovascular lesions induced by a 2% cholesterol diet in rabbits was mediated by a mechanism involving a component of hypothyroidism.
 ...
PMID:Failure of carbon disulfide and levothyroxine to modify the cardiovascular response of rabbits to a high-cholesterol diet. 308 26

A relationship was assessed between the amino acid composition of 9 protein sources or of their in vitro digestion products and total serum cholesterol in rats. Three animal proteins (casein, beef, fish) and 6 vegetable proteins (soy, pea, peanut meal, rapeseed, oatmeal, wheat gluten) were tested. The intact protein sources were submitted to an enzymatic proteolysis according to a new in vitro digestion method. Each protein source was hydrolyzed for 30 min with pepsin at pH 1.9, then with 10 mg pancreatin at basic pH in a dialysis cell. The digestion products diffused through the dialysis membrane of the cell and were collected by a circulating sodium phosphate buffer over a 6-h period. They were likely to correspond to end products luminal in vivo digestion. The aromatic and the basic amino acids were present in higher proportions in the digestion products than in the intact protein sources, reflecting the specificity of the proteolytic enzymes. Total serum cholesterol was measured on male Sprague-Dawley rats fed cholesterol-free or cholesterol-enriched (1% cholesterol, 0.5% cholic acid) semipurified diets containing protein sources. Total serum cholesterol ranged from 70 mg/dl with the pea diet to 98 mg/dl with the peanut meal diet in rats fed cholesterol-free diets and from 163 mg/dl with the wheat gluten diet to 313 mg/dl with the casein diet in rats fed the cholesterol-enriched diets. These results suggested no specific effect of protein from animal or vegetable origin on total serum cholesterol in rats. In rats fed cholesterol-enriched diets, significant correlations were observed between total serum cholesterol and tyrosine content or leucine/isoleucine ratio of digestion products. These correlations were stronger than those observed with intact protein sources.
Atherosclerosis 1986 Aug
PMID:Relationship between dietary proteins, their in vitro digestion products, and serum cholesterol in rats. 309 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>