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)

High levels of plasma triglycerides and very-low-density lipoproteins and low levels of high-density lipoproteins are consistently found in the metabolic cardiovascular syndrome. These changes are exaggerated postprandially. In the liver, synthesis and secretion of triglyceride-rich particles are increased. In addition, the removal capacity of plasma triglycerides is decreased, due to downregulation of lipoprotein lipase in skeletal muscles by hyperinsulinemia. Resistance to insulin-stimulated glucose uptake is believed to be the main pathogenetic factor. However, increased flux of free fatty acids from abdominally localized adipose tissue must also be considered when discussing pathogenesis. Treatment is primarily nonpharmacological, with diet and increased physical activity.
J Cardiovasc Pharmacol 1992
PMID:Lipoproteins, lipases, and the metabolic cardiovascular syndrome. 128 65

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.
J Cardiovasc Pharmacol 1990
PMID:Pathophysiology of hyperlipidemia in diabetes mellitus. 171 Jul 39

There is evidence that hypertensive patients frequently have other metabolic disorders, such as hyperlipidemia and diabetes mellitus. It is also known that the reduction in high blood pressure alone, disregarding the other cardiovascular risk factors, is unable to reduce mortality to the level of the general population. Moreover, the occurrence of metabolic side effects with some antihypertensive drugs deserves particular attention in the treatment of hypertension. Calcium antagonists seem to be devoid of untoward metabolic effects. In particular, several studies have shown that nitrendipine does not deteriorate glucose tolerance. We have evaluated the effects of nitrendipine on insulin response to i.v. glucose load: no change was observed after 2 months of treatment in both serum insulin levels and glucose percent removal rate in comparison to pretreatment values. No unfavorable change was detectable in the studies aimed at investigating the effects of nitrendipine on lipid metabolism parameters. We observed a 22% increase of the percent removal rate of a lipid emulsion (Intralipid) after nitrendipine (3.11 +/- 1.0 vs. 3.80 +/- 1.0%/min, p less than 0.03). This finding suggests a favorable effect of nitrendipine on triglyceride catabolism, possibly mediated by an interference with lipoprotein lipase activity. The metabolic neutrality of nitrendipine, therefore, leads to considering the usefulness of this drug in an antihypertensive treatment that should not disregard the global risk profile.
J Cardiovasc Pharmacol 1991
PMID:Metabolic neutrality in nitrendipine therapy. 172 52

Several drugs used for antihypertensive therapy may interact with lipoprotein metabolism and may increase associated coronary risk levels. beta-Blocker monotherapy with selective or nonselective beta-blockers without intrinsic sympathomimetic activity (ISA) usually increases serum triglyceride and decreases high-density lipoprotein (HDL), especially HDL2 cholesterol concentration. With the exception of the nonselective beta-blocker sotalol, beta-blocker therapy has little influence on the serum total cholesterol or low-density lipoprotein (LDL) cholesterol concentrations. The magnitude of these changes in serum lipids did not distinctly differ between selective and nonselective beta-blockers. Two beta-blockers possessing ISA, acebutolol, and pindolol did not show the increase in serum triglycerides and in serum total cholesterol or LDL cholesterol. Acebutolol showed the nonsignificant decrease in HDL cholesterol level. Pindolol with marked ISA exhibited the most favorable lipid profile, increasing serum HDL cholesterol and the ratio of HDL cholesterol to total cholesterol. The concentration of apolipoprotein A-I increased slightly during pindolol therapy. beta-Blockers with the exception of pindolol decrease the concentration of serum free fatty acids. beta-blocker therapy has little influence on the adipose tissue lipoprotein lipase activity, but lecithin cholesterol acyltransferase activity may increase during pindolol therapy.
J Cardiovasc Pharmacol 1985
PMID:Effects of beta-blockers on plasma lipids during antihypertensive therapy. 240 57

The effects of alpha 1-adrenergic receptor inhibition with doxazosin, and beta-blockade with propranolol on tissue lipoprotein lipases and plasma lipids were studied in rats. In rats fed a normal lab chow, doxazosin increased heart lipoprotein lipase activity (+14%), while propranolol had the opposite effect (-20%). These effects were not statistically significant when compared with nontreated controls, although the difference between the doxazosin and propranolol groups was significant (p less than 0.05). There were no significant effects on adipose tissue lipoprotein lipase activity or hepatic lipase activity. In rats fed a cholesterol-enriched diet there were similar but smaller effects on heart lipoprotein lipase activity (+5% and -12%, respectively). In these rats alpha 1-inhibition also tended to increase adipose tissue lipoprotein lipase (+14%) and hepatic lipase (+13%), while beta-blockade had the opposite effect (-20% and -9%, respectively). The lipase activities were significantly different between the treatment groups in liver and heart but not in adipose tissue. Doxazosin and propranolol did not affect plasma triglyceride or total cholesterol, but high-density lipoprotein cholesterol was increased during alpha 1-blockade (+24%).
J Cardiovasc Pharmacol 1987
PMID:Effects of doxazosin and propranolol administration on lipoprotein lipases in cholesterol-fed rats. 244 35

Relationships between lipoprotein fractions, lipoprotein lipase activities, thyroid hormones, and coronary lesion growth were studied among 35 male patients with severe coronary atherosclerosis, who had participated in the Leiden Intervention Trial, a lipid-lowering dietary intervention program. Coronary arteriography was performed at the beginning of the study and again 2 years later at its termination. The lesions were quantified using a computer-based analysis system to assess the progression rate of coronary lesions based on absolute arterial dimensions in a patient's coronary tree. For this reason an absolute coronary score was computed. Based on absolute coronary scores, patients could be divided into a no-lesion growth group (14 patients) and a progression group (21 patients). Lipoprotein fractions, lipoprotein lipases, and thyroid hormones were determined at the end of the trial. No significant differences were found between the no-lesion growth and progression groups for total cholesterol and low-density lipoprotein (LDL) cholesterol. In the progression group very-low-density lipoprotein (VLDL) cholesterol and triglycerides were significantly higher (p less than 0.05) and high-density lipoprotein (HDL) cholesterol was almost significantly lower (p = 0.058). Hepatic lipase (HL) values were significantly higher in the no-lesion growth group, when compared with the progression group, whereas lipoprotein lipase (LPL) values were not significantly different. Triiodothyronine (T3) was significantly lower (p less than 0.01) in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions. T3 and HDL cholesterol were also independently inversely related to coronary lesion growth.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1987
PMID:Diet and the role of lipoproteins, lipases, and thyroid hormones in coronary lesion growth. 244 40

One of the cells involved in lipid metabolism and thought to have adrenergic receptors is the macrophage. Low-density lipoprotein (LDL), once modified, can bind to modified LDL receptors on the macrophage. After binding to these receptors, LDL is internalized by a mechanism that is not controlled by feedback inhibition. This unregulated uptake results in massive cholesterol ester accumulation in atherosclerotic plaques. Macrophages secrete apolipoprotein E, a process that appears to be regulated by the cholesterol content of the macrophage, as well as by lipoprotein lipase. Macrophages are also thought to have receptors for high-density lipoprotein (HDL) on their surface, receptors that may play a key role in reverse cholesterol transport of cholesterol esters from the cells. Studies are being conducted to determine the effects of alpha 1-adrenergic activation on lipoprotein metabolism in these cells.
J Cardiovasc Pharmacol 1987
PMID:Role of macrophages in lipid metabolism. 244 41

Calcium antagonists and antihypertensive alpha-adrenergic and beta-adrenergic drugs may cause changes in plasma lipoprotein levels. Different mechanisms by which these antihypertensive agents effect cellular lipid metabolism have been proposed. The activity of lipoprotein lipase that determines the catabolism of very low density lipoproteins (VLDL) is decreased by the beta-blocker propranolol and increased by alpha 1-antagonists. The plasma cholesterol or low density lipoprotein (LDL) level is inversely associated with the number of LDL receptors. Catecholamines suppress the LDL receptor activity, thus leading to an increase in plasma cholesterol concentration. The calcium antagonist verapamil and the beta-blocker propranolol may increase LDL receptor activity either per se or by its antagonizing effect on the catecholamine action. The metabolism of high density lipoproteins (HDL) may be affected directly by catecholamines, which might increase HDL binding activity, thereby enhancing efflux of cholesterol from cells. Catecholamines inhibit cholesterol biosynthesis in extrahepatic cells. The effects are mediated by alpha 2- and beta 2-adrenergic receptors. Accordingly, the alpha 2-agonists clonidine and alpha-methyldopa mimicked and propranolol opposed the catecholamine action. In contrast, the alpha 1 antagonists indoramin, prazosin, and urapidil had no effect on cholesterol synthesis. The results provide evidence that calcium antagonists and various antihypertensive drugs, depending upon their action on beta- or alpha-adrenergic receptors, affect lipid metabolism differently. The metabolic effect may play a role in atherogenesis and may be of clinical importance when antihypertensive treatment is considered.
J Cardiovasc Pharmacol 1987
PMID:Effects of calcium antagonists and adrenergic antihypertensive drugs on plasma lipids and cellular cholesterol metabolism. 245 33

Several drugs used in the treatment of hypertension have been shown to affect lipid metabolism. A few studies have examined in detail the effects of calcium antagonists on blood lipids. We investigated the effects of nifedipine and nitrendipine on blood lipids using two experimental protocols. The first study was a double-blind, randomized, placebo-controlled trial to assess the effects of acute oral administration of nifedipine 10 mg on blood lipids in 10 patients (9 males, 1 female; age range 26-50 years) with mild hypertriglyceridemia. Serum triglycerides were not significantly affected (from 310 +/- 120 to 280 +/- 110 mg/dl 2 h after nifedipine) but a slight decrease was observed in patients with higher baseline levels. In the second study, an intravenous fat tolerance test (ivFTT, Intralipid 10%, 1 ml/kg body weight, as a bolus) was performed before and after chronic oral administration of nitrendipine 10 mg b.i.d. in 10 mild to moderate hypertensive patients (7 males, 3 females; age range 40-60 years). After nitrendipine treatment, the fractional removal rate (K2) of the lipid emulsion was significantly increased from 3.1 +/- 0.9 to 3.8 +/- 0.9% min (p less than 0.05). The main findings of these studies suggest that the secretion of lipoprotein lipase might be stimulated by calcium antagonists. Alternatively, the vasodilation produced by these compounds may influence triglyceride removal by expanding the capillary bed where the enzyme exerts its activity. In conclusion, calcium antagonists do not seem to cause unwanted side effects on blood lipids and apparently enhance triglyceride removal.
J Cardiovasc Pharmacol 1988
PMID:Acute and chronic effects of dihydropyridines on triglycerides in humans. 246 58

Doxazosin has been shown to lower serum cholesterol levels in the cholesterol-fed (0.75% in a synthetic diet that contains sucrose and cholic acid) C57BR/cdJ mouse. These studies show that the drug's main effect is to lower low-density lipoprotein (LDL) cholesterol and leave high-density lipoprotein (HDL) cholesterol levels unchanged. The drug had cholesterol-lowering effects in this model at doses down to 3 mg/kg. In order to determine if these effects are unique to selective alpha 1-inhibitors, other antihypertensives including hydralazine, papaverine, and captopril were investigated. None of the drugs has any effects on the plasma lipid metabolite levels. The effects of propranolol and polythiazide on plasma lipid levels were also examined in these mice. Propranolol had no effect, whereas the diuretic increased plasma cholesterol levels. Both propranolol and polythiazide increased plasma triglycerides. Doxazosin has been shown to inhibit cGMP phosphodiesterase in the laboratory. The effects of zaprinast, a cGMP phosphodiesterase inhibitor, were tested in order to determine if this property of the drug could be responsible for its lipid-lowering activity. The data show that there are no effects on plasma lipids in zaprinast-treated animals. Doxazosin treatment increased heparin-releasable lipoprotein lipase in fasted chow-fed mice. The drug was without effect on the activity of hepatic lipase present in the plasma after heparin release. No effects were observed on the tissue levels of either hepatic or lipoprotein lipases (heart or adipose tissue).
J Cardiovasc Pharmacol 1989
PMID:Effects of doxazosin and other antihypertensives on serum lipid levels and lipoprotein lipase in the C57BR/cdJ mouse. 247 Oct 10


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