Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein(a) or Lp(a), is a member of the plasma lipoproteins with general properties of LDL but with a protein moiety represented by apoB100 disulfide linked to apolipoprotein(a) or apo(a). Apo(a) is polymorphic in size; at present a total of 11 isoforms have been reported, but more are likely to be identified in view of the fact that at least 19 alleles of the apo(a) gene have recently been reported. There are remarkable variations in the plasma Lp(a) levels; but uncertainties still exist about the factors responsible for this variability. High plasma Lp(a) levels have been associated with an increased incidence of cardiovascular disease, mainly based on epidemiological evidence. Both atherogenic and thrombogenic potentials have been suggested; the first attributable to the LDL-like properties of Lp(a) and the other to the plasminogen-like characteristics of apo(a). From the mechanistic viewpoint in vitro studies suggest that the thrombogenic action may occur at the level of the endothelium whereas Lp(a) that localizes in the sub-endothelial intima is expected to undergo complexation with matrix components and favor the formation of the atherosclerotic plaque. How Lp(a) polymorphism relates to the postulated cardiovascular pathogenicity of this lipoprotein remains to be established.
Mol Cell Biochem 1992 Aug 18
PMID:Lipoprotein(a): its inheritance and molecular basis of its atherothrombotic role. 138 99

Glucocorticoid (GC) excess (Cushing's syndrome) is associated with hypertension in at least 70% of patients (in our series 89/130), independently of the subtype (pituitary or adrenal) and the duration, but not of the age of the patients. Cardiovascular damage is quite frequent in hypertensives, but is sometimes also present in normotensives. The mortality of patients with Cushing's syndrome is four times that of the general population when matched for age and sex, and much of this excess mortality is caused by cardiovascular disease. Hypertension remits in most of the patients after successful treatment, but may persist in some. Hypertension also occurs in 20% of patients treated with GC orally. The type of hypertension is independent of salt uptake, can not be controlled by spironolactone but is inhibited by a GC antagonist such as RU486. Experimentally-induced hypertension with oral cortisol (F) is associated with a rise in cardiac output, a fall in calculated total peripheral resistance, an increased forearm vascular responsiveness to exogenous norepinephrine, but no change in overall sympathetic tone, or in norepinephrine reuptake. The increased pressor responsiveness is probably due to local postsynaptic effector mechanisms in the resistance vessels, which could be important in phasic increases in neuronally mediated constrictor responses. Both in patients with Cushing's syndrome and in those on chronic GC treatment, the circadian blood pressure variations are absent or reversed. This may contribute to the deleterious effects of the GC excess on blood vessels. The vascular effects of the GC may be mediated by the activation of specific cardiovascular receptors, by modulating vascular transport systems, or by altered catecholamine or prostaglandin metabolism. GC may also act as mineralocorticoids (MC): in fact type 1 MC receptors are unable, in vitro, to distinguish between aldosterone and cortisol. The specificity-conferring mechanism of typical target organs for MC (e.g. kidney)--is thought to be due to the action of local 11-beta-hydroxysteroid dehydrogenase, which converts F to biologically inactive cortisone (E). When the activity of the enzyme is impaired (syndrome of apparent MC excess, liquorice or carbenoxolone administration), F acts as a MC and MC-hypertension with hypokalemia occurs.(ABSTRACT TRUNCATED AT 400 WORDS)
J Steroid Biochem Mol Biol 1992 Oct
PMID:Glucocorticoid-dependent hypertension. 139 Feb 89

Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease.
Mol Cell Biochem 1992 Aug 18
PMID:Genetic aspects of susceptibility to obesity and related dyslipidemias. 151 6

The increase of urinary albumin excretion has a predictive value for cardiovascular disease in insulin-dependent and non insulin-dependent diabetics. To study the relationship between urinary albumin excretion and serum lipids, 380 non insulin-dependent diabetics, 40 to 75 yr old, with urinary albumin excretion from 0 to 200 mg/l, and normal serum creatinine (less than 150 mumol/l), were surveyed. Urinary albumin excretion, was related positively to age (r2 = 0.014; p = 0.02), to systolic blood pressure (r2 = 0.073, p = 0.0001) and diastolic blood pressure (r2 = 0.052, p = 0.0001); a negative correlation existed with HDL-cholesterol (r2 = 0.043, p = 0.0001) and Apoprotein A1 (r2 = 0.044, p = 0.0001). A stepwise regression analysis was performed and resulted in three independently contributing variables related to urinary albumin excretion: First systolic blood pressure (F = 36), second Apoprotein A1 (F 24), third hemoglobin A1C (F = 6). The presence of hypertension or insulin therapy did not modify these findings. In conclusion, serum lipid seems an important determinant of urinary albumin excretion in non insulin-dependent diabetics.
Mol Cell Biochem 1992 Feb 12
PMID:Serum lipids and urinary albumin excretion in non insulin-dependent diabetics. 162 84

The molecular mechanisms of cardiac myocyte growth are relevant to important problems in cardiovascular disease. A cell culture model has been developed to explore the role of adrenergic hormones in cardiac myocyte growth and gene expression. Activation of a cardiac myocyte alpha 1-adrenergic receptor by catecholamines induces hypertrophic growth of neonatal rat cardiac myocytes and initiates selective increases in contractile protein gene transcription. These effects on growth and gene expression do not depend on contractile activity. The cardiac myocytes contain at least two subtypes of alpha 1-adrenergic receptors and at least three isoforms of protein kinase C (PKC). A distinct alpha 1 receptor subtype may mediate hypertrophy and gene transcription. Different isoforms of PKC are translocated to different intracellular sites on activation, and there is evidence that the beta-PKC isoform may be an element in the signal transduction pathway from an alpha 1 receptor at the surface to the cardiac myocyte nucleus. Growth regulation through a beta-adrenergic receptor can also be demonstrated in the culture model. The growth response mediated through a beta-adrenergic receptor differs in several respects from that transduced through an alpha 1-adrenergic receptor.
Mol Cell Biochem
PMID:Adrenergic hormones and control of cardiac myocyte growth. 165 95

Cardiovascular disease represents the major cause of morbidity and mortality in noninsulin-dependent diabetic patients. While it was once thought that atherosclerotic vascular disease was responsible for all of these adverse effects, recent studies support the notion that one of the major adverse complications of diabetes is the development of a diabetic cardiomyopathy characterized by defects in both diastolic and systolic function. Contributing to the development of the cardiomyopathy is a shift in myosin isozyme content in favor of the least active V3 form. Also defective in the noninsulin-dependent diabetic heart is regulation of calcium homeostasis. While transport of calcium by the sarcolemmal and sarcoplasmic reticular calcium pumps are minimally affected by noninsulin-dependent diabetes, significant impairment occurs in sarcolemmal Na(+)-Ca2+ exchanger activity. This defect limits the ability of of the diabetic heart to extrude calcium, contributing to an elevation in [Ca2+]i. Also promoting the accumulation of calcium by the diabetic cell is a decrease in Na+, K+ ATPase activity, which is known to increase [Ca2+]i secondary to a rise in [Na+]i. In addition, calcium influx via the calcium channel is stimulated. Although the molecular mechanisms underlying these defects are presently unknown, the possibility that they may be related to aberrations in glucose or lipid metabolism are considered. The evidence suggests that classical theories of glucose toxicity, such as excessive polyol production or glycosylation, appear to be insignificant factors in heart. Also insignificant are defects in lipid metabolism leading to accumulation of toxic lipid amphiphiles or triacylglycerol. Rather, the major defects involve membrane changes, such as phosphatidylethanolamine N-methylation and protein phosphorylation, which can be attributed to the state of insulin resistance.
Mol Cell Biochem 1991 Sep 18
PMID:Cardiomyopathy associated with noninsulin-dependent diabetes. 166 89

Corpulent male rats of the atherosclerosis prone JCR:LA-corpulent strain were fed diets supplemented with 10% by weight of olive oil or red fish oil. These rats are obese, with VLDL hyperlipidemia and marked insulin resistance. The diets were maintained to 9 months of age. Olive oil-fed rats had a 45% reduction in triglyceride concentrations with no significant changes in cholesterol or phospholipids. Red fish oil caused significant reduction in all lipid classes, with a 65% reduction in triglycerides and 35% reduction in cholesterol concentrations. Olive oil caused increases in the relative concentrations of oleic acid-containing triglycerides, while red fish oil preferentially enriched the longer chain fatty acids. There were no significant changes in insulin or glucose metabolism. The incidence of myocardial lesions, characteristic of the JCR:LA-cp strain, was unaltered by either oil-supplemented diet. These results, in a spontaneous animal model for cardiovascular disease, are consistent with other studies showing that diets rich in n-3 fatty acids do not, in themselves, confer protection against cardiovascular disease in animal models with genetically or experimentally induced lipid disorders.
Exp Mol Pathol 1991 Dec
PMID:Effect of dietary n-3 fatty acids on atherosclerosis prone JCR:LA-corpulent rats. 174 17

The myocardium consists of a muscle fibre array surrounded and interspersed by a network of connective tissue, principally collagen, which maintains the functional integrity of the heart. Changes in collagen composition may therefore contribute to altered ventricular function. Collagen composition was examined in cardiac tissue from 15 patients undergoing orthotopic cardiac transplantation. Of these, 10 had severely impaired left ventricular function due to coronary artery disease. The remaining five had dilated cardiomyopathy. Normal heart tissue was taken at autopsy from 25 patients who died of causes unrelated to cardiovascular disease. Left ventricular collagen concentration, estimated from hydroxyproline levels, increased from 48.6 +/- 4.1 mg/g dry weight of tissue in the control group to 95.3 +/- 9.7 mg/g (P less than 0.01) in patients with dilated cardiomyopathy and to 63.5 +/- 9.8 mg/g in the coronary artery disease group. This increase was attributable to an increase in absolute concentrations of both type I and III collagen, determined by separation of cyanogen bromide peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, there was a significant decrease in the proportion of type III collagen (compared with type I plus III) from 41.8 +/- 1.1% in controls, to 34.6 +/- 1.5% (P less than 0.01) in the coronary artery disease group and 35.8 +/- 2.8% (P less than 0.05) in the dilated cardiomyopathy group. These results suggest that excessive collagen production, with a preponderance of type I, occurs in these forms of myocardial disease, indicative of a remodelling of the collagen matrix, which, by increasing passive myocardial stiffness may contribute to impaired heart function seen in these groups of patients.
J Mol Cell Cardiol 1990 Oct
PMID:Enhanced deposition of predominantly type I collagen in myocardial disease. 209 38

We studied the inotropic and lusitropic responses to MCI-154 in 12 right or left ventricular trabeculae carneae isolated from 7 organ donors (non-cardiac) without known cardiovascular disease who met accepted criteria for brain death. Isometric tension was recorded from muscles superfused with a physiologic salt solution at 30 degrees C, and stimulated to contract at three-second intervals. Concentration-response curves were developed over a range of MCI-154 organs bath concentrations (10(-7) M to 3 x 10(-4) M; n = 9). Six experiments were conducted using 10(-6) M carbachol, a muscarinic agonist, in the presence of a maximally effective concentration of MCI-154 to test for dependence of tension development on cyclic adenosine monophosphate. Three experiments were conducted with MCI-154, 3 x 10(-5) M, in muscles loaded with the bioluminescent calcium indicator aequorin. MCI-154 produced a concentration-dependent rise in peak tension in the human muscle (positive inotropic effect), equivalent to 70% of the maximal response to calcium (P less than 0.001). Relaxation was enhanced (positive lusitropic effect), as evidenced by a fall in the time to 80% relaxation from 311 +/- 13 ms (baseline) to 248 +/- 15 ms at 10(-5) M (P less than 0.01). Aequorin studies showed the increase in tension to be accompanied by large increases in cystolic calcium, the principal mechanism of action. Carbachol caused MCI-154--induced maximum peak tension to decrease by 5 +/- 1%. While not excluding a cyclic adenosine monophosphate--mediated MCI action, this modest carbachol inhibition suggests the existence of additional mechanism(s) of action. MCI-154 had a negative lusitropic effect at high concentrations (greater than 10(-4)M) which may have been due to intracellular calcium overload, evidenced by the large amplitude aequorin signals. This does not exclude sensitization of the myofilaments to calcium as a possibility. Extrapolated to the in vivo setting, these experiments suggest that MCI-154 may be an effective positive inotropic agent in man.
J Mol Cell Cardiol 1989 Oct
PMID:Inotropic and lusitropic effects of MCI-154 (6-[4-(4- pyridyl)aminophenyl]-4,5-dihydro-3(2H)-pyridazinone) on human myocardium. 255 25

The purpose of this study was to determine whether daily running lengthens the life-span of animals dying prematurely due to cardiovascular disease. We used a strain of rat that is genetically hypertensive and obese and is reported to develop atherosclerosis (Exp. Mol. Pathol. 19: 53--60, 1973). These animals were divided into three groups consisting of runners exercised daily on treadmills from an early age life, food-restricted sedentary rats, and libitum eaters that were sedentary. This latter group had significantly higher average daily food intakes and body weights than either of the other two groups. The average life-span of both sedentary groups was significantly longer than the running group. Runners had a greater frequency of focal myocardial necrosis, but atherosclerosis was absent in all three groups. We speculate that daily running may have accentuated the development of factor s that may have contributed to the early death of runners.
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PMID:Longevity of exercising obese hypertensive rats. 744 Feb 77


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