Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kallikrein (Padutin-Depot) was administered to 20 patients with obliterative atherosclerosis of the lower limbs of the II degree (19 patients) and IV degree (1 patient). The drug was given in the daily dose of 40 U i.m. for 28 days. An effect of kallikrein on the distance in intermittent claudication, rate of pain relieve after walking the maximal distance, blood flow in the lower limbs, and on the index of circulating aggregates have been determined. Clinical improvement has been noted after a 4-week therapy with kallikrein. The drug in a single dose of 40 U activates plasma fibrinolytic system for 5 hours and decreases the number of circulating aggregates (2-5 h). The authors explain kallikrein action as the release of endogenous bradykinin, which subsequently releases two epithelial mediators, i.e. PFG1 and EDRF.
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PMID:[Kallikrein in the treatment of patients with obliterative atherosclerosis of the lower limbs and its mechanism of action]. 166 40

The plasma concentration of lipoprotein (a) (Lp(a] varies widely in humans, and elevated concentrations of this lipoprotein are correlated with progression of atherosclerosis. Structural studies of Lp(a) have revealed that it is a low density lipoprotein (LDL)-like particle containing a unique glycoprotein, apo(a), which shares extensive homology with plasminogen. The apo(a) portion of Lp(a) binds to the carboxy-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) or isolated apo(a) with fibronectin results in proteolytic cleavage of fibronectin which is, as visualized by gel electrophoresis and immunoblotting, distinct from that caused by plasmin or kallikrein. The proteolytic activity of apo(a) is of serine proteinase-type and displays specificity for arginine rather than lysine bonds. The molecular mechanism(s) underlying the association between Lp(a) and atherosclerosis remains an enigma.
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PMID:Interaction of lipoprotein(a) with fibronectin and its potential role in atherogenesis. 214 25

The effects of gemfibrozil on plasma prekallikrein, kallikrein inhibitors, kininogen and plasma lipids were investigated in 31 male subjects having either type IIA or IIB dyslipidaemia. During gemfibrozil use, plasma prekallikrein and kininogen were increased significantly while kallikrein inhibitors increased only slightly. Total cholesterol and triglycerides decreased while HDL cholesterol was increased. Changes in prekallikrein and HDL cholesterol were correlated, whereas no other significant correlations between changes in lipid and kinin parameters were seen. The observed changes in prekallikrein and kininogen possibly indicate a shift in the thrombo-haemorrhagic balance in favour for increased fibrinolysis. If so, the effects of gemfibrozil in prevention and management of atherosclerosis would not be solely due to correlation of the dyslipidaemia but also to protection against the accelerated coagulation tendency seen in type II dyslipidaemia.
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PMID:Plasma prekallikrein, kallikrein inhibitors, kininogen and lipids during gemfibrozil treatment in type II dyslipidaemia. 618 30

Some of the relatively easily measurable and possibly hypertension-associated parameters were evaluated in thirty normotensive young subjects divided into the PHT (either parent hypertensive) group and the PNT (both parents normotensive) group. In subjects of the PHT group, the platelet aggregating sensitivity to the arachidonic acid and the ratio of total cholesterol to HDL cholesterol were significantly (p less than 0.05) increased while urinary kallikrein excretion was decreased without simultaneously significant elevation of blood pressure. The enhanced platelet aggregating sensitivity to the arachidonic acid and the increased ratio of total cholesterol to HDL cholesterol suggest that subjects with a positive family history of hypertension might have a greater tendency to atherosclerosis and could contribute to the development of essential hypertension. Decreased urinary kallikrein excretion suggests that the vasodepressive activity of the kallikrein-kinin system might be inhibited in subjects with a positive family history of hypertension.
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PMID:Relation of family history of hypertension to platelet aggregation, ratio of total cholesterol to HDL cholesterol and urinary kallikrein excretion. 643 May 81

Genetic variations in the renin-angiotensin and kallikrein-kinin systems could prove to be significant pathophysiological mechanisms affecting coronary heart disease (CHD), particularly given the powerful vasoactivity of products such as angiotensin II and bradykinin. Indeed, studies show that angiotensin converting enzyme (ACE) gene polymorphism is associated with an increased risk of myocardial infarction and death, even in otherwise low-risk subjects. Genetic differences do not appear to be a risk factor for atherosclerosis or hypertension, however. Because ACE polymorphism modulates local production of angiotensin II, a powerful coronary vasoconstrictor, it may influence left ventricular mass in general as well as in coexisting disease states such as hypertension and cardiomyopathy. However, further study is needed to clarify the implications of ACE polymorphism in patients with left ventricular hypertrophy. Interactions between ACE and angiotensin II type-1 receptors may have clinical implications for preventing and managing CHD. Screening for genetic risk, as evidenced by certain variants in receptor coding sequence, may prove worthwhile if detrimental effects can be countered by drugs such as ACE inhibitors and angiotensin II receptor blockers. Given the important roles of angiotensin II and bradykinin as modulators of cellular growth and of vasoactivity, deleterious and beneficial effect at different stages of the atherosclerotic process and during acute events leading to myocardial infarction or sudden death can be suspected.
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PMID:Angiotensin I converting enzyme gene polymorphism and coronary heart disease. 886 31

Angiotensin (Ang) II plays an important role in cardiovascular homeostasis such as regulation of blood pressure and tissue remodeling. Alternative Ang II-forming pathways, independent of Ang I converting enzyme (ACE), have been reported. Several serine proteinases including kallikrein, cathepsin G and chymase appear to be involved in ACE-independent Ang II formation in vivo. Among them, biochemical analysis revealed that chymase is a highly efficient Ang II-forming enzyme with a high substrate specificity against Ang I and is rich in various human tissues. However, the pathophysiological roles of chymase have not yet been clarified. Recent reports from us and others indicated that chymase seems to be related to development of atherosclerosis, cardiomyopathy, remodeling of cardiovascular tissues, rheumatoid arthritis and etc. In this review article, the recent findings for chymase related to cardiovascular diseases are summarized.
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PMID:[Pathophysiological roles of human chymase]. 928

Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose column is brought about by electrostatic binding between the positive charges of apolipoprotein B in LDL and the negative charges of dextran sulfate cellulose. There is general agreement that the initial contact phase in the coagulation pathway may be activated by a negatively charged surface such as dextran sulfate cellulose, resulting in the generation of bradykinin. We investigated whether the increase in the generation of bradykinin during LDL adsorption is accompanied by the activation of endogenous production of nitric oxide (NO) in patients with peripheral atherosclerosis. LDL adsorption therapy was repeated ten times over a period of 3 months in ten peripheral atherosclerosis patients. Treatment significantly reduced serum total cholesterol and LDL cholesterol levels. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured the kinin-kallikrein system and plasma levels of NO in the same patients. The results showed that coagulation factors of the intrinsic pathway including high-molecular-weight kininogen and prekallikrein decreased markedly after initial adsorption compared with the levels before treatment. There was a marked increase in bradykinin and NO concentrations after the initial adsorption, compared with their levels before adsorption. Our results suggest that the generation of bradykinin and increased plasma levels of NO may contribute to the improvement in peripheral circulation after LDL adsorption in peripheral atherosclerosis patients.
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PMID:Removal of low-density lipoprotein from plasma by adsorption increases bradykinin and plasma nitric oxide levels in patients with peripheral atherosclerosis. 989 Jul 15

Experiments on 36 male rats with experimental hyperlipoproteinemia demonstrated that transcerebral exposure to impulse current (100 Hz, 2mA) aggravates atherogenic alterations, provokes hyperactivation of kallikrein-kinin system and unbalance of elastase inhibitory activity in the serum and myocardium. The latter may contribute to better vascular permeability for low-density lipoproteins, to development of edema of vascular intima, lability of cellular and lysosomal membranes with hydrolysis of elastine and collagen fibers of myocardial vessels and other organs. Transcerebral exposure to electromagnetic UHF field (40.68 MHz) is not hypolipidemic but has no negative effect on experimental atherosclerosis, promotes normalization of kallikrein-kinin system in the serum, activation of this system in the myocardium and cerebral cortex, correction of destructive processes in the serum and cerebral cortex with a risk of their development in the myocardium.
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PMID:[Changes in the proteinase-inhibitor system of rats with hyperlipoproteinemia during transcerebral exposures to a 100-Hz-frequency pulse current and to an ultrahigh-frequency field]. 1042 63

Tissue kallikrein cleaves kininogen substrate to produce vasoactive kinin peptides that have been implicated in the proliferation of vascular smooth muscle cells (VSMCs). To explore potential roles of the kallikrein-kinin system in vascular biology, we evaluated the effects of adenovirus-mediated human kallikrein gene delivery on the growth of primary cultured VSMCs and in balloon-injured rat artery in vivo. Kallikrein gene transfer into cultured rat VSMCs resulted in time-dependent secretion of recombinant human tissue kallikrein and inhibition of cell proliferation. Balloon angioplasty reduced endogenous rat tissue kallikrein mRNA and protein levels at the injured site. In rats that received adenovirus-mediated human kallikrein gene delivery, we observed a 39% reduction in intima/media ratio at the injured vessel after delivery compared with that of rats that received control virus (n=8, P<0.01). Icatibant, a specific bradykinin B(2) receptor antagonist, blocked the protective effect and reversed the intima/media ratio to that of the control rats (n=5, P<0.01). After gene delivery, human kallikrein mRNA was identified at the injured vessel and a 3-fold increase occurred in kininogenase activity. cAMP and cGMP levels in balloon-injured aorta increased significantly at 4, 7, and 14 days after kallikrein gene delivery, but icatibant abolished the increase. These results provide new insights into the role of the vascular kallikrein-kinin system and have significant implications for gene therapy to treat restenosis or atherosclerosis.
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PMID:Kallikrein gene delivery inhibits vascular smooth muscle cell growth and neointima formation in the rat artery after balloon angioplasty. 1045 35

Reduced activity of the endogenous fibrinolytic system contributes to intramural deposition of microthrombi in atherogenesis and to intraluminal deposition of thrombi leading to acute complications of atherosclerosis such as acute coronary syndromes. Endogenous fibrinolytic activity is predominantly regulated by the plasminogen activator inhibitor type 1 (PAI-1). Increased activity of PAI-1 leading to reduced endogenous fibrinolytic activity has been identified as an important independent risk factor for cardiovascular disease. Vascular endothelial cells form a barrier between the circulating blood with its dynamic balance between ongoing thrombosis and fibrinolysis and the subendothelial layers of the vascular wall with their prothrombotic activity. In addition, endothelial cells synthesize and secrete substantial amounts of plasminogen activators and their inhibitor PAI-1. Thus, endothelium plays an important role in the regulation of endogenous fibrinolysis. After describing the components of the endogenous fibrinolytic system and its interactions, this review focuses on the impact on endogenous fibrinolysis by the renin angiotensin system, the kallikrein kinin system, and type 2 diabetes mellitus. Investigations using transgenic and knock-out animal models--the results of which are also summarized--have improved our understanding of the interaction between endogenous fibrinolysis and endothelium. In each section of the review therapeutic implications and potentials are discussed.
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PMID:[Endothelium and endogenous fibrinolysis]. 1079 78


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