Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human heart in the fasting state extracts free fatty acids (FFA), glucose, lactate, pyruvate, and ketones from circulating blood. The utilization of FFA accounts for most of the oxygen consumed and energy produced at rest. Patients with angiographically demonstrable coronary artery disease and stable angina pectoris have a resting myocardial metabolism similar to that of normal individuals. During atrial pacing in normal persons, there is a significant enhancement of glucose uptake but that of FFA is unchanged, and the oxidation of carbohydrates accounts for more than 60% of the energy produced. In patients with stable angina, myocardial perfusion becomes regionally inadequate during stress. Despite the increase of myocardial glucose utilization, carbohydrate oxidation is negligible. Pyruvate will not be oxidized but in the presence of increased amounts of reduced coenzymes will be reduced to lactate. In addition, a greater amount of alanine will be released by the myocardium through the transamination of pyruvate, with a concomitantly greater uptake of glutamate that serves as the NH2 donor. In addition, glutamate may be used as an anaerobic fuel through conversion to succinate coupled with GTP formation. Although coronary hemodynamics, including myocardial perfusion, return to baseline within a few minutes after stress, a longer time course is needed for myocardial metabolism to become normal. In particular, myocardial utilization of exogenous glucose remains higher well after the normalization of hemodynamic parameters. This is more pronounced in postischemic myocardium, but it also occurs in nonischemic muscle, and glucose is presumably used for rebuilding glycogen stores that were depleted during ischemia.
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PMID:Metabolic markers of stress-induced myocardial ischemia. 202 52

The human heart in the fasting state extracts FFA, glucose, lactate, pyruvate, and ketone bodies from the systemic circulation. Of these substrates, FFA utilization accounts for the greater part of oxygen consumption and energy production. The oxidative use of lipid (FFA) and carbohydrate (glucose and lactate) fuels is reciprocally regulated through the operation of Randle's cycle. Feeding, by increasing both insulin and glucose concentration, shifts myocardial metabolism towards preferential carbohydrate usage, both for oxidative energy generation and for glycogen synthesis. During conditions of reduced oxygen supply, the oxidation of all substrates is decreased while anaerobic metabolism is activated. In patients with coronary artery disease and stable angina pectoris, lactate release in the CS can be demonstrated during pacing stress. However, this occurs in only 50% of patients, and no relationship can be demonstrated between lactate production and the severity of ischemia. In patients with chronic angina, a significant release of alanine in the CS and an increased myocardial uptake of glutamate could be demonstrated at rest and following pacing. These two phenomena result from increased transamination of excess pyruvate to alanine with glutamate serving as NH2 donor. In addition, release of citrate (a known inhibitor of glycolysis) in the CS can be demonstrated following pacing in patients with stable angina. The introduction of PET has made it possible to study regional myocardial perfusion and metabolism in humans noninvasively. Two basically different patterns of myocardial glucose utilization have been observed in patients with coronary artery disease studied at rest using 18F-flurodeoxyglucose. In patients with stable angina on exercise but studied at rest, regional myocar- dial glucose utilization was homogeneously low and comparable with that of a group of normals. In contrast, in patients with unstable angina, myocardial glucose utilization at rest was increased even in the absence of symptoms and ECG signs of acute ischemia. In patients with stable angina, a prolonged increase in glucose uptake could be demonstrated in the post-ischemic myocardium in the absence of perfusion abnormalities, and a state of chronic metabolic ischemia is proposed. PET imaging has also allowed prospective differentiation between viable and nonviable segmental function in patients with recent myocardial infarction and in those undergoing coronary artery surgery; in both cases viable segments have relatively maintained glucose uptakes, whereas nonviable segments have depressed glucose uptakes.
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PMID:Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by positron emission tomography. 268 79

Heparin cofactor II (HCII) is a serine proteinase inhibitor in human plasma that rapidly inhibits thrombin in the presence of dermatan sulfate or heparin. To understand the molecular mechanism for HCII deficiency in a patient with reduced circulating HCII antigen, we studied a Japanese patient with type I HCII deficiency who suffered from angina pectoris and coronary artery disease. Polymerase chain reaction (PCR)-based sequence analysis showed that the propositus' gene for HCII (HCII Awaji gene) had a thymine insertion after codon (GAT) for Asp88 in exon II, resulting in a frameshift mutation. Consequently, the abnormal HCII Awaji protein was suggested to have an altered amino acid sequence from position 89 and terminate at 107, thus being composed of the NH2-terminal one fifth of normal HCII and dysfunctional for thrombin inhibition. The molecular weight and pI value of HCII Awaji were calculated to be 12,040 and 3.6, respectively, without posttranslational modification. Mutagenic PCR followed by the Tsp509I digestion showed that a half of the PCR products derived from the propositus and his sister was cleaved, suggesting that his sister also has the same mutant allele. Crossed-immunoelectrophoresis and Western blot analyses of plasma and urine from the the propositus and of plasma from his sister did not provide evidence for the existence of the abnormal HCII, suggesting that little truncated HCII was circulating in the patient's blood. However, stable expression assay using human kidney 293 cells transfected with the expression vector containing cDNA encoding wild-type or Awaji-type HCII showed that mutant as well as wild-type HCII was secreted into culture medium normally. These results suggest that the abnormal HCII Awaji protein is secreted normally, but rapidly degraded in the circulating blood.
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PMID:Molecular and cellular basis for type I heparin cofactor II deficiency (heparin cofactor II Awaji). 856 24

The proband is a 50 year-old woman born from a consanguineous marriage. She has been suffering from angina pectoris since the age of 38 and underwent coronary bypass surgery for three-vessel disease at 48. The presence of low plasma levels of total cholesterol and high density lipoprotein (HDL) cholesterol (2.4 and 0.1 mmol/l) and apo AI (<15 mg/dl), associated with corneal lesions and a mild splenomegaly suggested the diagnosis of Tangier disease. However, none of the other features of Tangier disease, including hepatomegaly, anemia and peripheral neuropathy, were present. The analysis of the dinucleotide microsatellites located in chromosome 9q31 region demonstrated that the proband was homozygous for the alleles of D9S53, D9S1784 and D9S1832. The mother and son of the proband, both with low levels of HDL cholesterol, shared one of the proband's haplotypes, whereas neither of these haplotypes was present in the normolipidemic proband's sister. The sequence of ATP-binding cassette transporter 1 (ABC1-1) cDNA obtained by reverse transcription-PCR (RT-PCR) of total RNA isolated from cultured fibroblasts showed that the proband was homozygous for a C>T transition in exon 13, which caused a tryptophane for arginine substitution (R527W). This mutation was confirmed by direct sequencing of exon 13 amplified from genomic DNA. It can be easily screened, as the nucleotide change introduces a restriction site for the enzyme Afl III. R527W substitution occurs in a highly conserved region of the NH2 cytoplasmic domain of ABC1 protein. R527W co-segregates with the low HDL phenotype in the family and was not found in 200 chromosomes from normolipidemic individuals.
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PMID:A point mutation in ABC1 gene in a patient with severe premature coronary heart disease and mild clinical phenotype of Tangier disease. 1125 60