Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sympathetic nervous system plays a major role in the pathogenesis of essential hypertension and is mediated by the alpha and beta receptors. The alpha receptor is divided into two types, alpha 1 and alpha 2, based on response to epinephrine and norepinephrine. alpha 1-Adrenergic receptors have a high affinity for drugs such as prazosin, doxazosin, and terazosin, which act to reduce blood pressure by selective blockade of the receptor. These agents provide a rational approach to the treatment of hypertension by correcting elevated total peripheral resistance, the fundamental hemodynamic abnormality in essential hypertension. In contrast, early alpha-adrenergic receptor blockers nonselectively blocked both alpha 1 and alpha 2 receptors and were unsuitable as antihypertensive agents because they induced tachycardia and patients developed a tolerance to them rapidly. alpha 1-Adrenergic blockers also have beneficial effects on plasma lipoproteins, tending to decrease levels of triglycerides and cholesterol and increase levels of high-density lipoprotein (HDL) cholesterol and the HDL cholesterol/total cholesterol ratio. beta-Adrenergic blockers, such as propranolol and atenolol, have been shown to have an adverse effect on the lipid profile by tending to increase levels of triglycerides and decrease HDL cholesterol. A number of mechanisms contribute to these effects, in particular, adrenergic modulation of lipoprotein lipase and the triglyceride secretion rate. Doxazosin has been shown to increase the activity of LDL receptors, which may be partly responsible for its beneficial effect on plasma lipids and lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-adrenergic blockers: mechanism of action, blood pressure control, and effects of lipoprotein metabolism. 198 Feb 36

Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension.
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PMID:Multigenic human hypertension: evidence for subtypes and hope for haplotypes. 209 95

It is certain that atherosclerosis is multi-factorial. Amongst the numerous risk factors two are particularly important: hypertension and primary or secondary abnormalities of plasma lipids and lipoproteins (high levels of total cholesterol, LDL and VLDL cholesterol, triglycerides or VLDL triglycerides, apoprotein B, low levels of HDL cholesterol, apoprotein A1 and probably HDL2). On the basis of a general review of the literature, the authors evaluate the changes in lipids, lipoproteins and apoproteins induced by different beta-blockers. Overall, the most constant and most obvious (particularly in hyperlipidaemic patients) disturbances combine an increase in total triglycerides or VLDL triglycerides and a fall in HDL cholesterol. There is little change in total cholesterol or LDL cholesterol. Side effects seen with most beta-blockers, cardioselective or not, differ in degree from one drug to another. They are particularly marked with some (propranolol) while they are virtually absent with others (pindolol). The mechanism of action is discussed (essentially inhibition of extra-hepatic lipoprotein lipase activity). These findings would seem to lead to the following practical conclusions: 1) Before starting antihypertensive treatment it is important to confirm lipid and lipoprotein levels, particularly bearing in mind the epidemiological links between moderate essential hypertension and lipoprotein abnormalities, especially those with a component of hypertriglyceridaemia. 2) Lipid profile including estimation by precipitation of HDL cholesterol must be studied during antihypertensive therapy and if there is a marked and confirmed deterioration towards an "increased atherogenicity", it is reasonable to envision a change of the antihypertensive agent. With the some efficacy on blood pressure levels and general tolerance, the choice should favour drugs having the least unfavourable effects on lipoprotein metabolism.
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PMID:[Changes in lipids and lipoproteins caused by the beta-blocking agents used as antihypertensives]. 613 67

1 The effect on plasma lipids of pindolol given orally over a 6 month period to 20 patients with essential hypertension was studied. 2 During therapy an adipose tissue biopsy was taken from nine patients for the determination of lipoprotein lipase (LPL) activity and serum samples were taken for lecithin cholesterol acyltransferase (LCAT) assays. An additional biopsy and serum samples were taken after a 3 weeks' break in pindolol treatment. 3 Plasma free fatty acid and triglyceride concentrations remained similar during treatment. 4 Plasma total cholesterol was slightly lower (P less than 0.05) at 6 months than at 1 month. 5 HDL cholesterol concentration and the ratio of HDL to total cholesterol increased slightly, and the increase of HDL-cholesterol was significant (P less than 0.05) at 1 month. 6 LCAT activity was significantly higher (P less than 0.01) during pindolol treatment than after the break in it. No significant changes in adipose tissue LPL activities were found before and after the break of treatment.
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PMID:Effect of pindolol on serum lipids and lipid metabolizing enzymes. 710 59

In a previous open study on the metabolic effects of doxazosin in patients with essential hypertension, subgroup analysis indicated that subjects with an accumulation of risk factors for coronary heart disease (high VLDL triglycerides, low HDL cholesterol and high fasting blood glucose) seemed to benefit most from the metabolic actions of doxazosin treatment. Those results formed the basis of this double-blind, parallel-group study undertaken to elucidate the metabolic effects of 6 months of doxazosin and enalapril treatment in patients with both essential hypertension and hypertriglyceridemia. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method. Hemodynamic evaluation included measurements of office and ambulatory blood pressure and ultrasonic measurements of femoral artery blood flow. Both drugs significantly reduced both office BP and 24-h ambulatory BP. Office systolic BP was significantly better reduced by enalapril. Doxazosin, in contrast to enalapril, significantly increased insulin sensitivity (by 21%, P = .02). It also reduced serum-triglycerides (by 23%, P = .01), VLDL triglycerides (by 30%, P = .008) and VLDL cholesterol (by 24%, P = .02). This lipid-lowering effect of doxazosin was accompanied by an increase in both plasma lipoprotein lipase activity and the elimination rate of an intravenous fat emulsion load. Neither treatment significantly increased femoral artery blood flow. It is speculated that without measurably increasing blood flow in conduit vessels such as the femoral artery, doxazosin, by capillary recruitment, may prolong the transit time for the blood over the muscle bed, which could explain the increased glucose disposal and increased lipoprotein lipase activity.
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PMID:Metabolic effects of doxazosin and enalapril in hypertriglyceridemic, hypertensive men. Relationship to changes in skeletal muscle blood flow. 872 35

Essential hypertension is, at least in many subjects, associated with a decrease in insulin sensitivity, whereas glycemic control is (still) normal. Metaanalyses of hypertension intervention studies revealed different efficacy of treatment on cerebral (cerebrovascular accidents [CVA]) and cardiac (coronary heart disease [CHD]) morbidity and mortality. Although CVA were reduced to an extent similar to that anticipated, the decrease in CHD was less than expected. These differences are likely to be caused by the different impact of concomitant cardiovascular risk factors, such as dyslipidemia, impaired glucose tolerance, and non-insulin-dependent diabetes mellitus on CHD and CVA. Frequently these cardiovascular risk factors are ineffectively controlled in hypertensive patients, and moreover, some of the widely used antihypertensive agents have unfavorable side effects and further deteriorate these particular metabolic risk factors. Therefore, the metabolic side effects of antihypertensive treatment have received more attention. During the past few years, studies demonstrated that most antihypertensive agents modify insulin sensitivity in parallel with alterations in the atherogenic lipid profile. Alpha1-blockers and angiotensin converting enzyme inhibitors were shown to either have no impact on or even improve insulin resistance and the profile of atherogenic lipids, whereas most of the calcium channel blockers were found to be metabolically inert. The diuretics and beta-adrenoreceptor antagonists further decrease insulin sensitivity and worsen dyslipidemia. The mechanisms by which beta-adrenoreceptor antagonist treatment exert its disadvantageous effects are not fully understood, but several possibilities exist: significant body weight gain, reduction in enzyme activities (muscle lipoprotein lipase and lecithin cholesterol acyltransferase), alterations in insulin clearance and insulin secretion, and, probably most important, reduced peripheral blood flow due to increase in total peripheral vascular resistance. Recent metabolic studies found beneficial effects of the newer vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. In many hypertensive patients, elevated sympathetic nerve activity and insulin resistance are a deleterious combination. Although conventional beta-blocker treatment was able to take care of the former, the latter got worse; the newer vasodilating beta-blocker generation seems to be capable of successfully treating both of them.
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PMID:Antihypertensive therapy and insulin sensitivity: do we have to redefine the role of beta-blocking agents? 979 45

We sought to determine whether reductions in blood pressure in hypertensives after acute exercise persist for more than the 2 to 3 h found in controlled laboratory settings. Subjects (n = 11) were obese (32 +/- 4% body fat), sedentary (VO2max 27 +/- 4 mL/kg/min) 60 +/- 6-year-old men with stage 1 or 2 essential hypertension. Ambulatory blood pressure was recorded on 1 day preceded by 45 min of 70% VO2max treadmill exercise and on another day not preceded by exercise. Systolic blood pressure was lower by 6 to 13 mm Hg for the first 16 h after exercise (P < .05) compared to the day without prior exercise. Twenty-four-hour, day, and night average systolic blood pressures were significantly lower on the day after exercise. There was a trend for peak systolic blood pressure to be lower during the entire 24 h and the day portion of the recording; peak systolic blood pressure was significantly lower during the night portion of the recording after exercise. Systolic blood pressure load (percent of systolic blood pressure readings >140 mm Hg) was reduced during the entire 24 h and the day portion of the recording after exercise. Diastolic blood pressure was lower for 12 of the first 16 h after acute exercise (hours 0 to 4, 5 to 8, 13 to 16) (P < .05) compared to the day without prior exercise. Twenty-four-hour, day, and night average diastolic blood pressure was also significantly lower on the recording after exercise. Peak diastolic blood pressure was lower over the entire 24-h period. Diastolic blood pressure load (percent of diastolic blood pressure readings >90 mm Hg) was lower during the entire 24 h and the day portion of the day after exercise. Preliminary data also suggest that common genetic polymorphisms at the angiotensinogen, lipoprotein lipase, and angiotensin converting enzyme loci may affect the blood pressure-lowering response after acute exercise. Thus, in sedentary, obese hypertensive men a single aerobic exercise session reduced blood pressure enough to result in significantly lower 24-h average systolic, diastolic, and mean arterial blood pressure. This could result in a reduced cardiovascular load during the 24 h after acute exercise in older hypertensive men.
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PMID:Ambulatory blood pressure after acute exercise in older men with essential hypertension. 1067 70

Five candidate genes including the lipoprotein lipase, leptin, leptin receptor, alpha-adducin and beta3 adrenergic receptor were selected to examine their possible contribution to essential hypertension (EH) in a Chinese population. On each side of the candidate gene loci, one to two highly polymorphic microsatellite markers were genotyped in 474 subjects recruited from 106 hypertension nuclear families in Shanghai. Both parametric and nonparametric linkage analyses were carried out using GENEHUNTER (version 2.0) after genotyping. Extended transmission disequilibrium testing (ETDT) was also conducted to detect preferential transmission of alleles to affected offspring. We failed to find the linkage between all these loci and EH by either parametric or nonparametric analysis, nor did we detect any significant transmission disequilibrium by ETDT. Our findings provide no support for a significant contribution of these five genes to the pathogenesis of EH among Shanghai people.
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PMID:Linkage analysis of five candidate genes and essential hypertension in 106 Chinese nuclear families. 1257 19

Essential hypertension (EH) is a common late-onset disease that exhibits complex genetic heterogeneity. Human lipoprotein lipase (LPL) is a rate-limiting enzyme that regulates the catabolism of triglycerides (TG) and chylomicrons (CM). Since dyslipidemia is a common finding in hypertensive patients, the LPL gene is a logical candidate gene that could contribute to the development of hypertension. Using linkage analysis in 148 Chinese hypertensive families, we identified a region of linkage with systolic blood pressure (SBP) and diastolic blood pressure (DBP) that consisted of a 10.6-cM interval defined by markers D8S1145, D8S261, and D8S282 on chromosome 8, which maps between 31 to 41.6 cM from the 8p-telomere contained LPL gene, with statistically significant p values for the marker D8S261 (p = 0.0021 for SBP, and p = 0.0395 for DBP). In the qualitative-trait linkage analysis, evidence for linkage between the marker D8S1145 and EH was found (p = 0.0286). The transmission/disequilibrium test (TDT/S-TDT) also supported a significant linkage-disequilibrium of the allele 3 of D8S261 with EH (chi2 = 8.643, p < 0.01). Furthermore, the marker neurofilament light polypeptide (NEFL) (11 cM centromeric to the LPL gene) appeared to be in linkage with SBP and DBP (p = 0.0329 for SBP; p = 0.0319 for DBP). Additionally, two flanking markers for LPL, D8S511 (9.5 cM telomeric to the LPL gene) and D8S560 (3.2 cM centromeric to the LPL gene), also showed significant linkage with EH (p = 0.0036 for D8S511; p = 0.0115 for D8S560). Previous knowledge about the physiological involvement of LPL in blood pressure regulation and the present findings of variation near the LPL gene support the proposition that a region near the LPL gene or the LPL gene itself might contribute to the individual blood pressure variation in Chinese.
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PMID:Variation near the region of the lipoprotein lipase gene and hypertension or blood pressure levels in Chinese. 1286 2

To elucidate the mechanism of lipid metabolism in the genesis of essential hypertension (EH), we linked blood pressure (BP) phenotypes with the lipoprotein lipase (LPL) gene. Variance component and sib-pair linkage models were used to test the relationship of the polymorphisms in the LPL gene region and EH in 148 Chinese hypertensive families. Linkage evidence with systolic BP (SBP) and diastolic BP (DBP) was observed in a total population of 148 pedigrees with seven flanking microsatellite markers of the LPL gene, with a maximum two-point LOD score of 2.68 and a maximum multipoint LOD score (MLS) of 2.37 for SBP and a maximum MLS of 1.54 for DBP. Suggestive linkage results around this region were also obtained in northern and southern subsets by geographic distribution. In addition, quantitative-transmission/disequilibrium-test analyses showed that there was linkage between DBP and two single nucleotide polymorphisms in the LPL gene. This is the first report of linkage between LPL gene and DBP in the Chinese population. The LPL gene itself might explain our results or the LPL gene region might harbor some genes to explain the observed results to some degree and might contribute to the variation of BP in the Chinese population.
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PMID:Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees. 1512 90


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