Tissue plasminogen activator activity and inhibition in acute myocardial infarction and angiographically normal coronary arteries

Verheugt, Freek W. A.; Cate, J. W. Ten; Sturk, A.; Imandt, Leon; Verhorst, Patrick M.J.; Eenige, M. J. van; Verwey, Willem; Roos, J. P.

doi:10.1016/0002-9149(87)90851-4

Cited by 81 publications

(18 citation statements)

References 29 publications

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“…Clearty, investigators have identified reduced t-PA activity 34 or increased t-PA inhibitory activity 38 in the plasma of young survivors of acute myocardial infarction. Inhibition by Lp(a) of t-PA or plasminogen binding to fibrin with consequent abrogation of the enhancement of fibrinolytic activity may confer the potential for vascular occlusion to individuals with elevated levels of this unusual lipoprotein particle.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a), fibrin binding, and plasminogen activation.

et al. 1990

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Upoproteln(a) (Lp[a]> Is a complex plasma llpoproteln In which apollpoprotein (apo) B-100 Is covalerrtty linked by a dlsulfide bridge to a unique apollpoprotein, apo(a). The cDNA of apo(a) has recently been Isolated and sequenced, and a remarkable homology to human plasminogen has been noted. In this report, we demonstrate that, like plasminogen, Lp(a) binds to fibrin. In addition, Lp(a) competes wtth plasminogen and tissue-type plasminogen activator for fibrin binding. As a functional consequence of these binding properties, we show that Lp(a) attenuates the fibrin-dependent enhancement of tissue-type plasminogen activator activity against the native substrate, and does so as an uncompetrUve Inhibitor (K,=15 nM). 1 When present in high concentrations in plasma, Lp(a) correlates strongly with an increased risk for coronary artery disease.2 -5 Lp(a) is comprised of tow density lipoprotein in which apoKpoprotein (apo) B-100 is covalentty linked through a disutfide bridge to a unique apolipoprotefn, apo(a). While much information on the structure of Lp(a) has been obtained 6 ' 7 -8 and the cDNA sequence of apo(a) has been determined, 9 the actual function of Lp(a) and the mechanism of its atherogenlcity remain to be defined.The primary sequence of apo(a) has a striking similarity to ptasminogen 9 ; it contains: a serine protease domain that is 94% homologous with that of plasminogen, one copy of the kringte-5 region, and 37 copies of the kringte-4 domain. The structural homology to the serine protease active site of plasminogen notwithstanding, no latent enzymatic activity can be generated because of a crucial substitution of serine for arginine at the homologous activation site domain. 9 In the coagulation and fibrinotytic molecules in which they were first described, the kringle domains were identified as lysine-dependent fibrin binding regions. Plasminogen contains five kringles of which the first has the greatest binding affinity, 10 the second and third provide weaker affinity sites, and the fourth contains a site of intermediate affinity.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein(a), fibrin binding, and plasminogen activation.

et al. 1990

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“…Eighteen patients (9.8%) died after myocardial infarction. Age was not related to myocardial (15) Nifedipine (9), diltiazem (4), verapamil (2) ACE inhibitors (6) Captopril (1), lisinopril (2), perindopril (2), enalapril (1) b-adrenoceptor blockers (5) Oxprenolol (1), pindolol (1), atenolol (1), metoprolol (2) a 1 -adrenoceptor blockers (2) Urapidil (1), prazosin (1) Other (9) Diuretics (7), ibopamine (1), disopyramide (1) Central nervous system (53) Antidepressants (17) Imipramine (1), amitriptyline (2), mianserin (1), moclobemide (4), uvoxamine (2), trazodone (2),¯uoxetine (3), maprotiline (1), doxepine (1) Antipsychotics (1) Clozapine (1) Anti-migraine (35) Ergotamine (1), sumatriptan (33), methysergide (1) Respiratory system (15) b-sympatho-mimetics (7) Salbutamol (3), salmeterol (4), formoterol (2) Antihistamines (5) Terfenadine (1), cetirizine (2), cinnarizine (2) Other (3)…”

Section: Resultsmentioning

confidence: 99%

Drug-induced chest pain and myocardial infarction. Reports to a national centre and review of the literature

Ottervanger¹,

Wilson²,

Stricker³

1997

European Journal of Clinical Pharmacology

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“…Some studies have revealed a successful coronary thrombolysis with streptokinase or tissue plasminogen infusion that showed normal coronary arteries on angiography 8,9…”

Section: Discussionmentioning

confidence: 99%