Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma concentration of human lipoprotein(a) [Lp(a)] is correlated with the risk of heart disease. A distinct feature of the Lp(a) particle is the apolipoprotein (a) [apo(a)], which is associated with apoB-100, the main protein component of low-density lipoprotein. We now report that apo(a), which has extensive homology to plasminogen, binds to immobilized fibronectin. The binding of Lp(a) was localized to the C-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) with fibronectin resulted in fragmentation of fibronectin. The cleavage pattern, as visualized by gel electrophoresis and immunoblotting, was reproducibly obtained with Lp(a) purified from five different individuals and was distinct from that obtained upon proteolysis of fibronectin by plasmin or kallikrein. The use of synthetic peptide substrates demonstrated that the amino acid specificity for Lp(a) was arginine rather than lysine. The proteolytic activity of Lp(a) was localized to apo(a) and experiments with inhibitors indicated that the proteolytic activity was of serine proteinase-type.
 ...
PMID:Lipoprotein(a) binds to fibronectin and has serine proteinase activity capable of cleaving it. 253 57

Multiple components of the fibrinolytic mechanism (plasminogen, plasmin, antiplasmin, fibrinogen, fibrin degradation products) and factor II (prothrombin) levels were studied in 40 children with cyanotic congenital heart disease (CCHD) prior to corrective surgery. Seven of these were also studied post-operatively. A further 17 children were studied after corrective surgery only. Pre-operatively, increased fibrinolysis could bedemonstrated in only 7.5-12% of patients, and there was no correlation between the levels of fibrinolytic components and the severity of polycythemia or post-operative blood loss. There was no evidence of fibrinolysis post-operatively. Pre-operatively, low prothrombin levels were common (25%), were correlated with the amount of post-operative bloodloss and were restored to normal by corrective surgery. Hypoprothrombinaemia is one of the most significant haematological abnormalities in CCHD.
 ...
PMID:Pre- and post-operative studies of fibrinolysis and prothrombin in cyanotic congenital heart disease. 428 67

The time period after implantation of a ventricular assist device in patients with end-stage heart disease is complicated by hemorrhage in the early postoperative period and by thromboembolism in the later course. To investigate the pathophysiologic role of contact activation in 12 bridging patients (10 patients with a paracorporeal Berlin Heart [Berlin Heart GmbH, Berlin, Germany], 2 patients with an intracorporeal Novacor system [Novacor N100; Baxter, Oakland, CA]), hemostatic parameters were determined until heart transplantation or at least up to the 51st postoperative day. The following were observed: 1) In the early postoperative period, until day 15, levels of contact factors XI, XII, and prekallikrein were below normal, whereas levels of plasmin-a2-antiplasmin (PAP) complexes were elevated. Thrombin-antithrombin III (TAT) complexes, as well as platelet factor 4 and beta-thromboglobulin, significantly increased immediately after surgery. 2) In the later postoperative period, starting with the third postoperative week, an increase of factors XI, XII, and prekallikrein was observed. PAP and TAT complexes, as well as platelet factor 4 and beta-thromboglobulin, remained elevated. It is concluded that, in the early postoperative period, hemostasis is influenced mainly by an activation of the intrinsic contact system dependent fibrinolytic system with consumption of contact factors and increased levels of PAP complexes, whereas later system dependent fibrinolysis becomes less important, leading to a shift of the balance toward coagulation, with sustained prothrombin and platelet activation. This is in accord with the observed clinical complications (e.g., early postoperative bleeding, and thromboembolic events later on).
 ...
PMID:Pathophysiologic role of contact activation in bleeding followed by thromboembolic complications after implantation of a ventricular assist device. 857 16

The serum lipoprotein(a) [Lp(a)] level is a known risk factor for arteriosclerotic coronary artery disease. However, its association with restenosis after percutaneous transluminal coronary angioplasty (PTCA) is controversial. We hypothesized that the Lp(a) level is a significant risk factor for restenosis after angioplasty through a pathophysiological mechanism leading to excess thrombin generation or inhibition of fibrinolysis. We designed a prospective study of the relation of Lp(a) to outcome after PTCA, in which we measured selected laboratory variables at entry and collected clinical, procedural, lesion-related, and outcome data pertaining to restenosis. Restenosis was defined as >50% stenosis of the target lesion by angiography or as ischemia in the target vessel distribution by radionuclide-perfusion scan. Before the patients underwent PTCA, blood was obtained by venipuncture for measurement of Lp(a), total cholesterol, thrombin-antithrombin (TAT) complex, alpha2-antiplasmin-plasmin (APP) complex, and plasminogen activator inhibitor-1 (PAI-1). Evaluable outcome data were obtained on 162 subjects, who form the basis of this report. Restenosis occurred in 61 subjects (38%). The Lp(a) level was not correlated significantly with TAT, APP, PAI-1, or the TAT-APP ratio. Levels of TAT, APP, and PAI-1 were not statistically different in the patients with versus those without restenosis. The median ratio of TAT to APP was 2-fold higher in the restenosis group, and this difference approached statistical significance (P=0.07). Univariate analysis was performed for the association of clinical, lesion-related, and procedural risk factors with restenosis. Lp(a) levels did not differ significantly in the restenosis versus no-restenosis group, whether assessed categorically (>25 mg/dL versus <25 mg/dL) or as a continuous variable by Mann-Whitney U test. The number of lesions dilated and the lack of family history of premature heart disease were significantly associated with restenosis (P=0.002 and P=0.008, respectively). A history of diabetes mellitus was of borderline significance (P=0.055). By multiple logistic regression analysis, the number of lesions dilated was the only variable significantly associated with restenosis (P=0.03). We conclude that the number of lesions dilated during PTCA is a significant risk factor for restenosis, whereas the serum Lp(a) level was not a significant risk factor for restenosis in our patient population. The TAT to APP ratio merits further study as a possible risk factor for restenosis.
 ...
PMID:Lipoprotein(a) level does not predict restenosis after percutaneous transluminal coronary angioplasty. 971 35

Cardiovascular diseases are a group of disorders consisting importantly of coronary heart disease, peripheral arterial disease, cerebrovascular disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis and pulmonary embolism. Severe cardiovascular disease conditions lead to acute myocardial infarction and stroke. One of the reasons for this is formation of blood clots inside the vessel. Anticoagulants and antiplatelet drugs are used for managing cardiovascular diseases for a long time. However, they were unable to dissolve an existing thrombus. Fibrinolytic enzymes have become more substantial for treating cardiovascular diseases since they could lyse the fibrin clot within the blood vessel. Inability of plasma fibrinolytic system demands better thrombolytic drugs. Major thrombolytic enzymes belonging to plasminogen activators and plasmin like enzymes. Currently used fibrinolytic enzymes and their limitations are revisited in the present chapter. Reported enzymes from various sources with potential to be used as cardiovascular therapeutic is also discussed here.
 ...
PMID:Fibrinolytic Enzymes for Thrombolytic Therapy. 3148 6