Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity and immunocytochemical localization of cathepsin D in the frontal cortex were investigated in patients with Alzheimer disease (AD) and two groups of nondemented subjects; individuals with critical coronary artery disease (cCAD; > 75% stenosis) and non-heart disease controls (non-HD). The cathepsin D activity significantly increased with age in the non-HD population. No such age-related increase was observed in either AD or cCAD. Enzymatic activity was significantly increased in only the midaged, but not the older AD and cCAD subjects compared to controls. Immunocytochemical reactivity paralleled cathepsin D enzymatic activity. Frontal cortex neurons displayed an increased accumulation of cathepsin D immunoreactivity in aging (non-HD controls) with a further increase in cCAD, especially in the midaged group. Such immunoreactivity was markedly increased in AD. There was also an apparent age-related increase in the number of cathepsin D immunoreactive neurons in the non-HD population and a disease-related increase in only the mid-aged AD and cCAD subjects compared to controls. Senile plaques (SP) occurred in all AD patients, many cCAD, and a few of the oldest non-HD subjects, and they were immunoreactive to cathepsin D in each group. The data suggest a possible relationship between activation of cathepsin D and SP formation in AD, cCAD, and aging.
Mol Chem Neuropathol 1996 Sep
PMID:Cortical cathepsin D activity and immunolocalization in Alzheimer disease, critical coronary artery disease, and aging. 888 36

Gender specific differences in cardiovascular disease are largely mediated by sex hormones. The use of estrogens significantly reduces the overall incidence of heart disease in postmenopausal women. Beneficial effects of estrogens on plasma lipoprotein levels are clearly established. However, these do not explain the magnitude of risk reduction seen in clinical studies. Thus additional and currently unknown functions of estrogens must be operative. Elucidation of the exact estrogen action in the heart will have important implications in the treatment of cardiovascular disease. It will probably enhance the therapeutic repertoire in treating heart disease, the most common cause of death in industrialized countries. We will review the current understanding of the function of estrogens in the heart and discuss potential strategies on how to apply these data to clinical practice.
Mol Cell Biochem
PMID:Estrogen effects in the heart. 890 88

The Na,K-ATPase is of major importance for active ion transport across the sarcolemma and thus for electrical as well as contractile function of the myocardium. Furthermore, it is receptor for digitalis glycosides. In human studies of the regulatory aspects of myocardial Na,K-ATPase concentration a major problem has been to obtain tissue samples. Methodological accomplishments in quantification of myocardial Na,K-ATPase using vanadate facilitated 3H-ouabain binding to intact samples have, however, made it possible to obtain reliable measurements on human myocardial necropsies obtained at autopsy as well as on biopsies of a wet weight of only 1-2 mg obtained during heart catheterisation. However, access to the ultimately, normal, vital myocardial tissue has come from the heart transplantation programs, through which myocardial samples from cardiovascular healthy organ donors have become available. In the present paper we evaluate the various values reported for normal human myocardial Na,K-ATPase concentration, its regulation in heart disease and the association with digitalization. Normal myocardial Na,K-ATPase concentration level is found to be 700 pmol/g wet weight. No major variations were found between or within the walls of the heart ventricles. During the first few years of life a marked decrease in myocardial Na,K-ATPase concentration is followed by a stable level obtained in early adulthood and normally maintained throughout life. In patients with enlarged cardiac x-ray silhouette a significant positive, linear correlation between left ventricular ejection fraction (EF) and Na,K-ATPase concentration was established. A maximum reduction in Na,K-ATPase concentration of 89% was obtained when EF was reduced to 20%. Generally, heart failure associated with heart dilatation, myocardial hypertrophy as well as ischaemic heart disease is associated with reductions in myocardial Na,K-ATPase concentration of around 25%. During digoxin treatment of heart failure patients a further reduction in functional myocardial Na,K-ATPase concentration of 15% has been found. Thus, the total reduction in functional myocardial Na,K-ATPase concentration in digitalised heart failure patients may well be of the magnitude 40%. In conclusion, it has become possible to quantify human myocardial Na,K-ATPase in health and disease. Revealed reductions are in heart failure of importance for contractile function, generation of arrhythmia and for digoxin treatment.
Mol Cell Biochem
PMID:Human myocardial Na,K-ATPase concentration in heart failure. 897 67

The identification of genetic loci involved in most forms of congenital heart disease has been hampered by the complex inheritance patterns of these disorders. Atrioventricular canal defects (AVCDs) are most commonly associated with Down syndrome, although non-syndromic cases also occur. Non-syndromic AVCDs have been attributed to multifactorial inheritance. However, the occurrence of a few kindreds with multiple affected individuals has suggested that a major genetic locus can account for the disorder in some families. We have used a combination of DNA pooling and shared segment analysis to perform a high density screen of the entire autosomal human genome in an extended kindred. In so doing, we have identified a genetic locus on chromosome 1 shared by all affected individuals. Our data demonstrate the existence of a congenital heart defect susceptibility gene, inherited as an autosomal dominant with incomplete penetrance, involved in AVCD. Furthermore, our data demonstrate the power of using key isolated kindreds in combination with high density genomic screens to identify loci involved in complex disorders such as congenital heart defects.
Hum Mol Genet 1997 Jan
PMID:Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis. 900 79

Human apolipoprotein(a), a risk factor for heart disease, has over 80% sequence identity to plasminogen. Plasminogen contains five distinct kringle domains plus a catalytic protease subunit. Human apo(a) consists of multiple copies (the number varies in individuals) of a domain resembling kringle 4, a single copy of a domain resembling kringle 5, and a protease-like domain. The recently cloned hedgehog version of apolipoprotein(a), which contains 31 nearly identical copies of plasminogen kringle 3 and lacks a protease domain, has prompted us to investigate the evolutionary history of the apolipoprotein(a) gene in mammals. Our analysis supports the nonfunctionality of the human apolipoprotein(a) protease domain, and a single (or multiple) duplication of plasminogen gene before mammal radiation, which originated apolipoprotein(a) in mammals.
J Mol Evol 1997 Feb
PMID:Apolipoproteins(a): a puzzling evolutionary story. 906 84

Activated microglial cells are concentrated in senile plaques characteristic of Alzheimer's disease. Such accumulations of activated microglia may contribute towards neurodegeneration via production of cytokines and free radicals. Studies suggesting a link between Alzheimer's disease and heart disease led us to study microglia immunohistochemically, using monoclonal antibody LN-3, in age-matched nondemented humans with and without heart disease. Using a qualitative staging system for assessing morphological changes occurring in microglia, we found higher microglial activation in the brains of subjects with heart disease than in those without it. Lectin histochemical examination of brains from rabbits maintained on a high-cholesterol diet also revealed increased microglial activation and leukocyte infiltration. Collectively our observations from humans and rabbits suggest that hypercholesterolemia and heart disease accelerate brain aging, and that the formation of senile plaques may be the end result of progressive microglial activation that occurs with aging.
J Mol Med (Berl) 1997 Feb
PMID:Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits. 908 23

Myocardial Na+,K(+)-ATPase was studied in patients with aortic valve disease, and myocardial Na+,K(+)- and Ca(2+)-ATPase were assessed in spontaneously hypertensive rats (SHR) and hereditary cardiomyopathic hamsters using methods ensuring high enzyme recovery. Na+,K(+)-ATPase was quantified by [3H]ouabain binding to intact myocardial biopsies from patients with aortic valve disease. Aortic stenosis, regurgitation and a combination hereof were compared with normal human heart and were associated with reductions of left ventricular [3H]ouabain binding site concentration (pmol/g wet weight) of 56, 46 and 60%, respectively (p < 0.01). Na+,K(+)- and Ca(2+)-ATPases were quantified by K(+)- and Ca(2+)-dependent p-nitrophenyl phosphatase (pNPPase) activity determinations in crude myocardial homogenates from SHR and hereditary cardiomyopathic hamsters. When SHR were compared to age-matched Wistar Kyoto (WKY) rats an increase in heart-body weight ratio of 75% (p < 0.001) was associated with reductions of K(+)- and Ca(2+)-dependent pNPPase activities (mumol/min/g wet weight) of 42 (p < 0.01) and 27% (p < 0.05), respectively. When hereditary cardiomyopathic hamsters were compared to age-matched Syrian hamsters an increase in heart-body weight ratio of 69% (p < 0.001) was found to be associated with reductions in K(+)- and Ca(2+)-dependent pNPPase activities of 50 (p < 0.001) and 26% (p = 0.05), respectively. The reductions in Na+,K(+)- and Ca(2+)-ATPases were selective in relation to overall protein content and were not merely the outcome of increased myocardial mass relative to Na+,K(+)- and Ca(2+)-pumps. In conclusion, myocardial hypertrophy is in patients associated with reduced Na+,K(+)-ATPase concentration and in rodents with reduced Na+,K(+)- and Ca(2+)-ATPase concentrations. This may be of importance for development of heart failure and arrhythmia in hypertrophic heart disease.
Mol Cell Biochem 1997 Apr
PMID:Reduced concentration of myocardial Na+,K(+)-ATPase in human aortic valve disease as well as of Na+,K(+)- and Ca(2+)-ATPase in rodents with hypertrophy. 908 35

By sequestering activator calcium, the sarcoplasmic reticulum (SR) plays the central role in the excitation-contraction (E-C) cycle of cardiac muscle. Hence, functional changes in the SR in diseased myocardium might critically determine its mechanical characteristics. Previously, we demonstrated that both Ca2+ release and uptake were increased in SR isolated from hearts showing compensatory left ventricular (LV) hypertrophy taken from pressure-overloaded rats. However, it has not been elucidated whether such alterations also occur in the volume-overloaded myocardium. Rats in which volume-overloaded hypertrophy had been induced by aortocaval shunt 12 weeks prior to the investigation were compared to sham-operated controls in terms of SR Ca2+ uptake and release, and density of Ca2+ releasing channels (ryanodine receptors, RyR). Isometric tension and intracellular Ca2+ transients were also measured using the bioluminescent Ca2+ indicator, aequorin, in isolated LV papillary muscles. The extent of hypertrophy was verified by measuring the ratio of biventricular weight to body weight. In vivo, the aortocaval shunt rats showed normal LV contractility and slightly depressed LV relaxation, indicating a compensatory (adaptive) stage of LV function. In contrast, Ca2+ release, uptake, and maximal number of [3H]-ryanodine binding sites were all significantly lower in aortocaval shunt rats than in controls. Both the Ca2+ transients and isometric relaxation of the isolated myocardium were significantly prolonged in aortocaval shunt rats, though their amplitudes were similar in the two groups. Thus, the volume-overloaded cardiac hypertrophy, even at its hemodynamically compensatory (adaptive) stage, (i) was accompanied by abnormal Ca2+ handling, as indicated by prolonged intracellular Ca2+ transients and isometric tension traces, (ii) seems to involve subcellular mechanisms related to decreases in SR Ca2+ release and uptake functions, as well as to a decrease in the number of RyR. Therefore, changes in the intracellular processes underlying cardiac E-C coupling, including SR function, precede the development of this type of heart disease.
J Mol Cell Cardiol 1997 Apr
PMID:Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats. 916 Aug 62

To evaluate whether polymorphisms in the 5' region of the apolipoprotein(a) gene alter the risk for myocardial infarction, 289 Russian male patients with myocardial infarction (MI) and 284 subjects in a control group were investigated regarding the distribution of pentanucleotide repeats (PNRs) at position -1373 and a C/T transition at position +93. For detection of the C/T (+93) allele, we developed a rapid, nonisotopic method by mismatch PCR-mediated site-directed mutagenesis and restriction enzyme digestion. We observed significant differences in prevailing alleles with over eight (TTTTA) repeats among MI patients, including those with MI younger than 55 years of age. We observed the prevalence of the T (+93) allele in children without a family history of CHD compared to young MI patients. These findings support the notion that PNR alleles with over eight (TTTTA) repeats may play a pathogenic role, and the T (+93) allele may have a protective effect for the inherited predisposition to heart disease.
Biochem Mol Med 1997 Aug
PMID:Comparative analysis of apo(a) gene alleles: distribution of pentanucleotide repeats in position -1373 and C/T transition in position +93 among patients with myocardial infarction and a control group in St. Petersburg, Russia. 925 86

Apoptosis is a potentially important myocardial response to pathology including ischemia and reperfusion. Na-H exchange (NHE) represents an important mechanism for mediating such injury. The present study was done to determine if NHE inhibition can affect early apoptosis in an acute model of ischemia and reperfusion. Isolated rat hearts were subjected to zero-flow ischemia for various durations with or without subsequent 30 min of reperfusion. Nick-end-labelling of biotin-dUTP (TUNEL staining), as well as DNA extraction followed by agarose gel electrophoresis, were used to semiquantify apoptotic cells and identify DNA laddering, respectively. Apoptosis first appeared after 10 min of ischemia and reached a maximum level after 30 min. The number of apoptotic cells after 30 min of ischemia was 31 +/- 3 per 100 high power microscopic fields, whereas in reperfused hearts the number of cells was 34 +/- 3. To determine the effect of NHE inhibition, hearts were pretreated 15 min prior to ischemia with HOE 642, a potent and specific inhibitor of the isoform (NHE-1) found in myocardium. HOE 642 significantly reduced the number of apoptotic cells in the ischemic and reperfused heart to 2 +/- 1 and 6 +/- 1, respectively (P<0.05 from untreated hearts). DNA laddering was not observed with electrophoretic DNA analysis, likely owing to the small number of apoptotic cells involved. Hearts recovered nearly 100% of function in both groups, although there was a significantly higher recovery after 1 and 2 min of reperfusion in those hearts treated with HOE 642. Our study shows that apoptosis, albeit very mild in nature, can be rapidly induced in isolated hearts by a relatively brief period of ischemia without reperfusion, which can be markedly attenuated by the NHE inhibitor HOE 642. The ability of HOE 642 to markedly attenuate apoptosis may be important in terms of understanding the drug's cardioprotective properties as well as the overall role of NHE in heart disease.
J Mol Cell Cardiol 1997 Nov
PMID:A rapid ischemia-induced apoptosis in isolated rat hearts and its attenuation by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide). 940 90


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