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)

Untreated acromegaly is associated with an increased cardiovascular morbidity and mortality. The contribution of altered lipid metabolism remains unclear. We investigated the relationship between serum apolipoprotein(a) (apo(a)) and growth hormone (GH) levels in 15 patients with acromegaly before and during treatment with octreotide, a long-acting somatostatin analogue, 288-600 micrograms/day s.c., for 6 months. Before treatment serum apo(a) was significantly elevated in acromegalic patients (geometric mean being 323 U/l vs. 142 U/l in controls (n = 92; P < 0.01)). Octreotide treatment resulted in significant reductions in serum apo(a) concentration (F = 7.22; P < 0.01; geometric mean being 232 U/l and 248 U/l at 3 months and 6 months respectively) and apo(a) concentrations on treatment were not significantly different from control values. There were significant reductions in serum GH (F = 7.30; P < 0.01), insulin growth factor 1 (IGF1) (F = 31.4, P < 0.001) and insulin (F = 4.57; P < 0.05) concentrations. Plasma glycosylated haemoglobin levels were unchanged. Apo(a) levels correlated with serum GH (r = 0.450; P < 0.01) but showed no correlation with basal insulin concentrations. Serum HDL cholesterol increased on treatment (F = 4.29; P < 0.05). Triglycerides were reduced only in the 12 patients without diabetes mellitus (F = 4.75; P < 0.05). No significant change in LDL cholesterol occurred. Our findings suggest that apo(a) may constitute another cardiovascular risk factor in untreated acromegaly and that GH may be involved in the regulation of circulating apo(a) concentration.
Atherosclerosis 1993 Dec
PMID:Serum apolipoprotein(a) correlates with growth hormone levels in Chinese patients with acromegaly. 814 41

The relationship of Lp(a) with manifestations of coronary heart disease (CHD) has not been studied extensively in women. There is little information as to the association of the unique Lp(a) apolipoprotein moiety (apo(a)) with CHD in either men or women. We therefore assessed the association of the apo(a) polymorphism and of Lp(a) with first acute myocardial infarction (MI) in a population-based case-control study in Jewish residents of Jerusalem between the ages of 25 and 64. The patients consisted of 238 men and 47 women hospitalized for a first acute MI in the 4 hospitals of Jerusalem serving the population (70% response rate among all first MI patients). The control subjects comprised 318 men and 159 women sampled from the national population registry and who were free of CHD (75% response). Lp(a) and apo(a) were measured in plasma stored at -20 degrees C for 6-24 months. Among men, plasma Lp(a) concentrations were higher in cases than controls in both univariate and multivariate analyses. The elevated risk was limited to the upper fifth of the Lp(a) distribution (unadjusted odds ratio = 1.65, P < 0.01 vs. the lower four quintiles, multivariable odds ratio = 1.82, P < 0.01). Among women, Lp(a) was not elevated in acute MI patients. Apo(a) isoforms with a B, S1 or S2 band (associated with higher Lp(a) values and having lower molecular weights) were more prevalent in female MI cases than controls (unadjusted odds ratio = 2.5, P = 0.016). This association could not be attributed to the higher Lp(a) concentrations associated with these isoforms and was not seen in men. In conclusion, our study points to an association of the apo(a) isoforms with acute MI in women, not evident in this population sample in men. Previously described associations of elevated Lp(a) with acute MI were confirmed in men but not in women. While the role of chance and inadequate statistical power cannot be excluded, the suggestion of a sex difference in the strength of these associations deserves further investigation, as does the question of whether apo(a) phenotype contributes to risk independently of Lp(a) level.
Atherosclerosis 1993 Jan 25
PMID:Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population. 845 57

Cardiovascular diseases are the leading cause of disability and mortality in western countries. Lipoprotein(a) [Lp(a)] is now considered an independent risk factor for atherosclerosis, and might consequently be related to longevity and/or disability. In the context of a study on metabolic and anthropometric parameters in a sample of Italian octo-nonagenarians, Lp(a) and apo(a) isoforms were evaluated. One-hundred and fifty Italian octo-nonagenarians were classified as free-living or disabled, according to Katz's index, and compared to 91 healthy control adults. All the study subjects were recruited from a valley (Val Vibrata valley) near Teramo, in the central part of Italy. The median Lp(a) concentration of the whole group was 17 mg/dL (range 1-161 mg/dL), which is much higher than the values observed in Caucasian populations. No differences were detected between the octo-nonagenarian group (median 16 mg/dL, range 1-126 mg/dL) and the control group (median 19.5 mg/dL, range 1-161 mg/dL), nor between the free-living and the disabled groups. Apo(a) isoforms were similarly distributed among free-living, disabled and control subjects. While our findings suggest that Lp(a) plasma levels and apo(a) isoforms are not factors associated with longevity or disability, we cannot exclude that the low incidence of other major risk factors for atherosclerosis in our free-living octo-nonagenarians hampered the full expression of the lipoprotein(a) atherogenic potential, and thus allowed the achievement of a very old age in a good healthy status, even in carriers of high Lp(a) levels or small apo(a) isoforms.
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PMID:Lipoprotein(a) plasma levels and apo(a) isoforms are not associated with longevity or disability in a sample of Italian octo-nonagenarians. Associazione Medica Sabin. 871 6

The concentration of lipoprotein(a) [Lp(a)] in human plasma is largely genetically determined and is inversely correlated to the size of apolipoprotein(a) [apo(a)]. Additionally, Lp(a) values are relatively stable within individuals and are only marginally susceptible to therapeutic treatment. The aim of our study was to evaluate the effect of exogenous testosterone on plasma Lp(a) concentration. The study was carried out on 19 healthy men who were receiving weekly intramuscular injections of 200 mg testosterone enanthate. Lp(a) values were determined at multiple time-points by a double monoclonal antibody-based enzyme immunoassay. This method is not sensitive to variation in Lp(a) size and the values are expressed in nmol/l. Apo(a) size isoforms were determined by agarose gel electrophoresis followed by immunoblotting. No correlation was found between the baseline Lp(a) values and the baseline values of testosterone or estradiol. The Lp(a) response to testosterone treatment varied widely among subjects and was dependent upon the pretreatment Lp(a) concentration. For 10 subjects with low Lp(a) values (< 25 nmol/l), no significant decrease in Lp(a) was observed while, for the nine individuals with Lp(a) values > 25 nmol/l, there was a significant and consistent reduction in Lp(a) ranging from 25 to 59%. Lp(a) levels returned to baseline values following cessation of testosterone administration. Apo(a) size polymorphism did not appear to play a role in the determination of Lp(a) response to testosterone.
Atherosclerosis 1996 Apr 26
PMID:Testosterone-induced suppression of lipoprotein(a) in normal men; relation to basal lipoprotein(a) level. 872 15

Lipoprotein (a) (Lp(a)) is a LDL-like lipoprotein with an additional highly polymorphic glycoprotein--apolipoprotein (a) (apo(a)). Apo(a) bears great homology with plasminogen. Lp(a) is synthesized by liver and its degradation may be carried out by a nonspecific process. Apo(a) isoform size and plasma Lp(a) levels are mainly determined by apo(a) gene. Lp(a) can easily be deposited in arterial wall. It promotes growth of smooth muscle cells and inhibits fibrinolysis. These could be the mechanisms by which Lp(a) accelerates atherosclerosis and thrombosis. The physiological role of Lp(a) has not been clearly understood.
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PMID:[Research progress in lipoprotein (a): aspects of biochemistry and molecular biology]. 873 79

To evaluate whether a high level of lipoprotein(a) (Lp(a)) is a risk for the development of coronary heart disease (CHD), 94 Japanese patients and 64 age-matched Japanese controls, diagnosed after coronary angiography (CAG), were analyzed with special reference to the relations between the degree of atherosclerosis, Lp(a) levels and the apolipoprotein(a) (apo(a)) genotypes. the degree of atherosclerosis was evaluated based on CAG findings in the following three ways: the number of diseased vessels, the Gensini score, and the presence or absence of vascular ulcers and/or irregular outlines of coronary stenotic lesions. Apo(a) protein sizes and the pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the apo(a) gene were analyzed. Multivariate predictors for the number of diseased vessels were, in decreased order of significance, plasma Lp(a) levels, history of smoking, hypertension, diabetes mellitus, and body mass index (BMI). Independent factors associated with the Gensini score were Lp(a) levels, BMI, hypertension, and diabetes mellitus. A negative association of Lp(a) levels with apo(a) protein sizes, and higher Lp(a) levels in those homozygous for an allele with 8 8 (TTTTA)-repeats, was found in both the controls and patients. In decreasing order of significance, apo(a) protein sizes, the degree of atherosclerosis, the genotype of the pentanucleotide repeat, and gender were independent predictors of Lp(a) levels in stepwise regression models. Apo(a) protein sizes were a significant predictor, and the genotype homozygous for the 8 (TTTTA)-repeats was a possible predictor, for the degree of atherosclerosis in CHD. These findings support the notion that a high Lp(a) level is a risk for the development of atherosclerosis in CHD.
Atherosclerosis 1996 Jun
PMID:Apolipoprotein(a) and pentanucleotide repeat polymorphisms are associated with the degree of atherosclerosis in coronary heart disease. 878 49

In human plasma with no detectable lipoprotein (a) (Lp(a)) levels, platelet-activating factor acetylhydrolase (PAF-AH) is associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) with a distribution of 70 and 30%, respectively. We used a density gradient ultracentrifugation procedure to study the distribution of PAF-AH among lipoproteins in plasma containing Lp(a). Lp(a) was migrated as a broad band in the density region of d = 1.050-1.100 g/ml, independently of its isoform size. In plasma with Lp(a) levels 30-40 mg/dl or 80-100 mg/dl the PAF-AH activity migrated in this density region was 4 or 9% higher as compared to plasma having Lp(a) levels < 8 mg/dl (P < 0.05 or P < 0.02, respectively). Enrichment of plasma with the dense LDL5 subfraction, significantly increased the enzyme activity distributed in this density region. The physicochemical properties of the Lp(a)-associated PAF-AH activity were similar to those reported for the LDL-associated enzyme. However, the kinetic constants in small Lp(a) isoforms were significantly higher compared to large ones. Isoform F had apparent Km = 117 +/- 9 mumol/l and Vmax = 94 +/- 5 nmol/mg protein per min, and isoform S2/S3 had apparent Km = 36 +/- 9 mumol/l and Vmax = 25 +/- 5 nmol/mg protein per min. Removal of apolipoprotein (a) (apo(a)) from Lp(a) by reductive cleavage with dithiothreitol, slightly affected the amount of PAF-AH existing on Lp(a) since, only 15 +/- 5% of the total enzyme activity dissociated from its particle after density gradient ultracentrifugation. During Cu(2+)-induced Lp(a) oxidation, the PAF-AH activity decreased from 10.90 +/- 2.30 nmol/mg per min to 2.57 +/- 0.56 nmol/mg per min 4 h after the initiation of the oxidation (P < 0.001). The apparent Km of the enzyme remained essentially unchanged during oxidation, whereas Vmax was significantly decreased from 58.6 +/- 7.8 nmol/mg protein per min to 38.2 +/- 8.7 nmol/mg protein per min (P < 0.03). An extensive hydrolysis of the endogenous phosphatidylcholine (PC) to lysophosphatidylcholine (lyso-PC) was observed during Lp(a) oxidation, since the Lyso-PC/sphingomyelin molar ratio at the end of oxidation (0.55 +/- 0.09) was significantly higher than that before oxidation (0.19 +/- 0.01, P < 0.001). Our results show that the existence of Lp(a) in plasma alters the distribution of PAF-AH among the other lipoproteins. Apo(a) seems to affect the association of the enzyme with Lp(a) but does not bind itself to PAF-AH. During Lp(a) oxidation, the PAF-AH activity decreases whereas an extensive hydrolysis of the endogenous PC to Lyso-PC is observed which is possibly due to the PAF-AH activity.
Atherosclerosis 1996 Aug 23
PMID:PAF-acetylhydrolase activity of Lp(a) before and during Cu(2+)-induced oxidative modification in vitro. 883 34

Prospective case-control studies investigating lipoprotein(a) [Lp(a)] as a risk factor for atherosclerosis have measured Lp(a) in samples stored frozen up to nearly 20 years. We therefore prospectively examined the influence of long-term plasma sample storage on measured values, depending on the molecular weight of apolipoprotein(a) [apo(a)] isoforms. Apo(a) phenotyping was performed in 310 plasma samples, and Lp(a) was measured after 3 and 28 months of storage at -80 degrees C. The values of both measurements correlated significantly for both low- and high-molecular-weight apo(a) phenotypes (r = .97 and r = .98, respectively, P < .001). Nevertheless, we detected on average a small decrease of 4.83% from mean +/- SD (median) 21.24 +/- 23.54 (11.10) mg/dL to 20.02 +/- 21.72 (10.55) mg/dL, which was statistically significant (P < .001). The absolute and relative Lp(a) decrease over time became larger with a decreasing number of kringle IV repeats of apo(a) (P < .05), and Lp(a) decreased markedly more in subjects with low-molecular-weight compared with those with high-molecular-weight apo(a) isoforms (-3.26 versus -0.46 mg/dL, P < .05). More than 70% of the absolute Lp(a) decrease in the total sample was caused by samples with low-molecular-weight apo(a) isoforms, which represented only 27% of the sample. Low-molecular-weight apo(a) isoforms are reportedly more frequent in patients with atherothrombotic disease compared with control subjects. Measurement of Lp(a) in several-year-old frozen samples is therefore likely to result in a preferential decrease and false lower Lp(a) concentrations in patient groups compared with control groups. The negative results of some prospective studies with retrospective measurement of Lp(a) may be caused by such an artifact.
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PMID:Lipoprotein(a) in stored plasma samples and the ravages of time. Why epidemiological studies might fail. 897 63

Analyses of 1163 samples from the San Antonio Family Heart Study revealed several elements of genetic control of lipoprotein(a) (Lp(a)) concentrations in Mexican Americans. Apolipoprotein(a) (apo(a)) isoform size variation was inversely related to Lp(a) concentrations and explained about 22% of total phenotypic variation. Segregation analyses suggested the existence of a major gene that influenced an additional 41% of total Lp(a) variation. A G-->A polymorphism in the LPA promoter was in strong disequilibrium with apo(a) isoform size, but did not contribute a significant amount of additional information about Lp(a) variation. However, about 25% of variation in Lp(a) concentrations was influenced by additive polygenic effects, which include the effects of null phenotype alleles. Altogether, these genetic components explained 89% of Lp(a) variation, similar to heritability estimates made in several other studies. Apo(a) size variation and the major gene (explaining a total of about 62% of Lp(a) variation) were linked to each other and, as expected, to the plasminogen locus. Thus, together with the well-established null phenotype allele, these different genetic factors represent at least three distinct elements of control exerted at the LPA locus, which encodes the apo(a) protein.
Atherosclerosis 1997 Feb 10
PMID:Characterization of the genetic elements controlling lipoprotein(a) concentrations in Mexican Americans. Evidence for at least three controlling elements linked to LPA, the locus encoding apolipoprotein(a). 905 Jul 79

Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta-thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta-thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, -46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same 'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.
Atherosclerosis 1997 May
PMID:Plasma lipoprotein composition, apolipoprotein(a) concentration and isoforms in beta-thalassemia. 918 Feb 53


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