Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Silent myocardial ischemia (SI), an asymptomatic manifestation of coronary artery disease (CAD), was identified in 10% of apparently healthy nonsmoking, nondiabetic older (60 +/- 7 years, mean +/- SD) men with normal plasma cholesterol levels. We hypothesized that in the absence of other major risk factors for CAD, the men with SI would have reduced plasma levels of high density lipoprotein (HDL) and HDL2 subspecies due to an upper-body fat distribution (waist-to-hip ratio [WHR]), hyperinsulinemia, and abnormal postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Compared with 47 normal control subjects of similar age, obesity, and maximal aerobic capacity, the 18 men with SI had higher plasma triglyceride (TG) (162 +/- 71 versus 102 +/- 39 mg/dl, p less than 0.001) and lower HDL-C (33 +/- 6 versus 37 +/- 7 mg/dl, p less than 0.02) levels with no difference in low density lipoprotein cholesterol level. The HDL2b and HDL2a subspecies measured by gradient gel electrophoresis were also lower in the men with SI (p less than 0.01). The plasma glucose and insulin responses during an oral glucose tolerance test were the same in both groups. Postheparin plasma HL activity was significantly higher in 12 men with SI than in 41 control subjects (34 +/- 8 versus 27 +/- 10 mumol/ml.hr-1, p less than 0.03) and was correlated with log insulin area (r = 0.36, p less than 0.05) and WHR (r = 0.32, p less than 0.05) in the control subjects but not in the men with SI. In the control group, the percent HDL2b subspecies was correlated inversely with postheparin plasma HL activity (r = -0.46, p less than 0.01, n = 41) as well as WHR (r = -0.49, p less than 0.001, n = 47) and log insulin area (r = -0.37, p less than 0.05, n = 47) but not in the men with SI. Postheparin LPL activity was the same in both groups of men and did not correlate with HDL, WHR, insulin, or plasma TG levels. As the control subjects and men with SI had comparable degrees of abdominal obesity and hyperinsulinemia, these results suggest that the reduced HDL-C levels in men with SI may be related to elevations in HL activity. Thus, abdominal obesity, hyperinsulinemia, elevated TG levels, and low HDL-C and HDL2 subspecies levels may predispose these older men to atherosclerosis.
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PMID:Reduced HDL2 cholesterol subspecies and elevated postheparin hepatic lipase activity in older men with abdominal obesity and asymptomatic myocardial ischemia. 161 6

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
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PMID:Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. 220 Jul 27

Twenty-five CAPD patients were given gemfibrozil in increasing doses for a total of 14 weeks. Parameters of lipid metabolism including serum total cholesterol, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol triglyceride, apolipoprotein A-1, apolipoprotein B, postheparin lipoprotein lipase, and hepatic lipase activities were measured before the commencement, at every increment in the dose of gemfibrozil and 4 weeks after discontinuation of therapy. Gemfibrozil normalized the deranged parameters of lipid metabolism. Thus, with treatment, serum triglyceride, and total cholesterol, LDL cholesterol and apo B decreased, whereas serum HDL cholesterol, HDL2, and HDL3 (predominantly the latter subfraction), hepatic lipoprotein lipase activities increased. Apo A-1 did not change significantly. Even in normotriglyceridemic patients serum HDL cholesterol increased. The side effects consisted of muscle aches and a significant rise in serum CPK. Gemfibrozil produced a significant decrease in gamma-GT activities. A possible mechanism for the interconversion between HDL2 and HDL3 that resulted in a preferential increase in the latter was discussed. It was concluded that gemfibrozil, in a dose not exceeding 300 mg twice a day favorably improved the risk factor for ischemic heart disease in CAPD patients.
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PMID:Gemfibrozil improves abnormalities of lipid metabolism in patients on continuous ambulatory peritoneal dialysis: the role of postheparin lipases in the metabolism of high-density lipoprotein subfractions. 250 77

There is a very high probability that lipoprotein metabolism plays a central role in the etiology of coronary heart disease. In sedentary persons one way to favorably alter lipoprotein metabolism and possibly delay the progression of coronary atherosclerosis is by an increase in their habitual physical activity. More physically active persons tend to have lower plasma triglycerides and very low density lipoprotein concentrations, and a greater high-density lipoprotein mass due to higher concentrations of the subfraction HDL2 and apoprotein A-I. Plasma low-density lipoprotein concentrations usually are not significantly reduced by exercise unless accompanied by weight loss, but there may be important changes in the distribution among the low-density subfractions. These exercise effects are most likely mediated by alterations in the activity of enzymes involved in the synthesis, transport and catabolism of the various lipoproteins including lipoprotein lipase, hepatic lipase and lecithin: cholesterol acyltransferase. In healthy persons as well as in patients with ischemic heart disease, diabetes and renal failure, an increase in moderate-intensity, endurance-type activity requiring an expenditure of approximately 4 MJ (1,000 kcal) per week usually produce favorable lipoprotein changes. Above this level a dose-response relationship exists, with greater changes occurring up to energy expenditures of 19 MJ (4,500 kcal) per week.
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PMID:The influence of exercise training on plasma lipids and lipoproteins in health and disease. 353 12

Antihypertensive drugs are expected to have a lipid-lowering effect for use in treating ischemic heart disease. We evaluated the effect of (+)-N-(6-amino-3-pyridil)-N'-[(1S,2R,4R)-bicyclo-[2.2.1]hept-2-yl] -N"- cyanoguanidine hydrochloride (AL0671), a newly synthesized cyanoguanidine-derivative potassium channel opener, on serum lipid and lipoprotein levels in obese Zucker rats, a genetically engineered model of type IV hyperlipidemia. AL0671 dose-dependently decreased systolic blood pressure in obese Zucker rats. Serial administration (for 1 or 2 weeks) of AL0671 (5 mg/kg/day) significantly decreased serum total triglyceride, chylomicron and very-low-density lipoprotein levels with increasing high-density lipoprotein cholesterol, whereas low-density lipoprotein levels did not change. AL0671 (5 mg/kg/day) increased lipoprotein lipase activities 4-fold and hepatic triglyceride lipase activities 3-fold in postheparin plasma. Another urea-derivative compound, AL0674, whose potassium channel-opening activity is diminished, did not affect serum lipid and lipoprotein levels. These results suggested that AL0671 activates both lipoprotein lipase and hepatic triglyceride lipase activities through its potassium channel-opening activity followed by decreasing triglyceride-rich lipoproteins in genetically obese hyperlipemic rats. Therefore, AL0671 might be beneficial in the treatment of hypertensive patients with hypertriglyceridemia (probably with insulin resistance).
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PMID:A possible mechanism of action of a new potassium channel opener, AL0671, on lipid metabolism in obese Zucker rats. 799 82

Danazol, a weakly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints. Early reports indicated that the drug had little effect on plasma lipid (cholesterol and triglyceride) levels but recently concern has been expressed over more subtle changes reported in plasma lipid and lipoprotein metabolism after danazol treatment. Therapy produces a rapid reduction in high density lipoprotein (HDL) cholesterol (particularly in the putatively cardioprotective HDL2 subfraction) coupled with a rise in the pro-atherogenic low density lipoprotein (LDL). These apparently unwanted actions are balanced against a possibly beneficial reduction in the atherogenic lipoprotein(a) fraction. The mechanism of these changes induced by danazol is unknown but probably relates to effects on hepatic lipase, LDL receptor and lecithin cholesterol acyl transferase activity. While it is prudent to recognize the potential detriment that may follow these perturbations, concern is only warranted where therapy is prolonged (> 12 months) or given to subjects with a high background risk of ischemic heart disease.
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PMID:Action of danazol on plasma lipids and lipoprotein metabolism. 820 70

The potential long-term impact of danazol on coronary risk hinges on its effect on lipoprotein metabolism rather than its influence on total plasma lipids. Danazol may exert a regulatory influence on three key processes in lipoprotein metabolism: hepatic lipase activity; low-density lipoprotein receptor function; and lecithin:cholesterol acyl-transferase activity. Danazol decreases plasma fibrinogen and lipoprotein (a) levels, promotes fibrinolysis and causes a rise in plasminogen. Such changes are beneficial as they inhibit the process of thrombosis. Androgenic properties of danazol produce effects of plasma lipids and lipoproteins which oppose estrogen-induced changes. The usual recipients of danazol therapy are premenopausal females, in whom the absolute risk of ischemic heart disease is low. If the drug were shown to increase ischemic heart disease risk, detrimental factors must be weighted against its considerable and proven clinical benefits.
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PMID:Danazol and plasma lipoprotein metabolism. 852 71

In women, serum lipid levels and the incidence of myocardial ischemia increase after menopause. Deficiency of estrogen is believed to be the cause of these epidemiological phenomena. On the other hand, hormone replacement therapy(HRT), has prevailed in developed countries. Estrogen is replaced to ease climacteric disorders, and retard bone loss. Many clinical studies cleared the effect of HRT on lipids, in which total and LDL-C (cholesterol) decreased, and HDL-C increased. TG increased by conjugated equilin estrogen but not by transdermal estradiol. In our study, hepatic triglyceride lipase(HTGL) was suppressed by HRT, but lipoprotein lipase(LpL) was not suppressed. HRT decreases coronary artery diseases, but it is still controversial whether HRT is efficient in patients who already have heart disease.
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PMID:[Efficacy of hormone replacement therapy on hyperlipidemia]. 1063 24

Atherosclerosis is the main cause of death in the world through causing ischemic heart disease (IHD). Altered serum lipid level is the most important risk factor for coronary artery disease (CAD). Many studies reveal a strong inverse association between low levels of high density lipoprotein cholesterol (HDL-C) and increased risk of IHD. On the other hand, plasma levels of HDL-C has a strong hereditary basis. This review focuses on recent data about genetic defects that reduce the level of HDL-C. In order to investigate possible genes linked to low HDL-C disorder, we reviewed previous studies; we searched current medical literature from September 1990 through January 2013 for the genetics causes of low HDL-C levels. Genetic defects in ATP binding cassette protein (ABCA1), apolipoprotein (APO) A1, lecithin cholesteryl acyl transferase, Lipoprotein lipase (LPL), and angiopoietin-like 3 proteins (ANGPTL3) associated with low HDL-C. Other potentially important candidates involved in low HDL-C syndromes are metabolic disorders including sphingomyelin phosphodiesterase 1 and glucocerebrosidase. Also Molecular variations in many genes such as ABCAI and APOAI, TRIB1 and Apo E, lipoprotein lipase (LPL), WW domain-containing oxidoreductase (WWOX), Hepatic lipase (HL), lecithin cholesteryl acyl transferase and some linkage analysis have been associated with reduced HDL-Status. Low HDL-C syndrome has a strong genetic basis and is correlated with an increased risk of CAD.
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PMID:Genes associated with low serum high-density lipoprotein cholesterol. 2491 32