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Thromb Res. 1991 Nov 15;64(4):493-501.
Gemfibrozil predictably lowers triglycerides but does not significantly change plasminogen activator inhibitor activity in hypertriglyceridemic patients with a history of thrombosis.

Haire WD.

Department of Internal Medicine, University of Nebraska Medical Center, Omaha.

Impaired fibrinolysis due to high plasminogen activator inhibitor levels is present in patients with a variety of thrombotic diseases. Plasminogen activator inhibitor levels correlate with triglyceride levels and are elevated in patients with hypertriglyceridemia. Treatment of asymptomatic hypertriglyceridemic patients with diet or medication results in improvement of fibrinolytic parameters. To determine if similar improvements in fibrinolysis occur during treatment of hypertriglyceridemia in patients with a history of venous thrombosis and impaired fibrinolysis due to high plasminogen activator inhibitor levels, 5 patients were given gemfibrozil. Triglyceride levels and fibrinolytic response to venous occlusion were determined before and after 30 days of treatment. Gemfibrozil therapy resulted in a predictable decrease in triglyceride levels in all patients, a reduction that was statistically significant (p = 0.04). There was no significant change in fibrinolytic variables during gemfibrozil therapy. Independent factors appear to control the plasminogen activator inhibitor and triglyceride levels in patients with a history of venous thrombosis.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1788834&dopt=Abstract




J Lipid Res. 1995 Jun;36(6):1294-304.
Gemfibrozil significantly lowers cynomolgus monkey plasma lipoprotein[a]-protein and liver apolipoprotein[a] mRNA levels.

Ramharack R, Spahr MA, Hicks GW, Kieft KA, Brammer DW, Minton LL, Newton RS.

Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.

Eight male cynomolgus monkeys (Macaca fascicularis) on a normal chow diet were orally administered gemfibrozil daily using a weekly rising dose protocol for 3 weeks (50, 125, and 200 mg/kg per day). At these drug doses, Lp[a] levels were reduced: 83.7% +/- 3.2 (SEM), (P < 0.024); 63.7% +/- 4.1 (P < 0.013); and 36.2% +/- 1.1 (P < 0.002), respectively, of pretreatment values. Lp[a] reduction was directly related to blood gemfibrozil concentration (range 36-428 microM, r = 0.969) and occurred without concomitant changes in apolipoprotein B. Three weeks posttreatment Lp[a] levels returned to pretreatment values. A specific ribonuclease protection assay demonstrated that liver apolipoprotein[a] (apo[a]) mRNA expression was decreased in all animals to an average of 19.1% +/- 3.0 (P < 0.0026), of pretreatment values after the 200 mg/kg treatment, whereas, albumin, apolipoprotein A-I, apolipoprotein E, and glyceraldehyde-3-phosphate dehydrogenase mRNAs were unchanged. Lp[a] levels were unaffected by gemfibrozil in HepG2 cells permanently transfected with an apo[a] 10-kringle cDNA construct containing partial 5'- and 3'-untranslated sequences and under control of a constitutive CMV promoter. However, both Lp[a] and apo[a] mRNA in primary cynomolgus monkey hepatocytes were coordinately lowered in a dose-dependent fashion by gemfibrozil. Thus, Lp[a] can be regulated by gemfibrozil at the level of apo[a] mRNA expression.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7666007&dopt=Abstract




Arch Intern Med. 1994 Nov 28;154(22):2605-9.
Antibody against oxidized low-density lipoprotein predicting myocardial infarction.

Puurunen M, Manttari M, Manninen V, Tenkanen L, Alfthan G, Ehnholm C, Vaarala O, Aho K, Palosuo T.

National Public Health Institute, Helsinki, Finland.

BACKGROUND: Oxidation of low-density lipoprotein is believed to be an important step in the pathogenesis of atherosclerosis. The purpose of the present study was to determine whether antibody against oxidized low-density lipoprotein, reported to be associated with the progression of carotid atherosclerosis, is predictive of cardiac death and nonfatal myocardial infarction. METHODS: Serum samples from 135 cases and their controls, drawn at entry from middle-aged dyslipidemic men participating in the Helsinki Heart Study, a 5-year coronary primary prevention trial with gemfibrozil, were tested for immunoglobulin G class antibodies against oxidized low-density lipoprotein by enzyme-linked immunosorbent assay. RESULTS: The mean antibody level, expressed in optical density units, was significantly higher in cases than in controls (0.412 vs 0.356, P = .002). After adjustment for age, smoking, blood pressure, and high-density lipoprotein cholesterol level, there was a 2.5-fold increased risk (95% confidence interval, 1.3 to 4.9) of a cardiac end point in the highest tertile of antibody level vs the lowest tertile (P = .005 for trend). CONCLUSIONS: Elevated levels of antibodies against oxidized low-density lipoprotein were predictive of myocardial infarction. The effect was independent of low-density lipoprotein cholesterol levels, and the joint effect was additive. Elevated antibody levels modified the effects of classic coronary risk factors.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7979858&dopt=Abstract













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