Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A thirty-year-old man who had sudden onsets of unconsciousness, right hemiparesis and conjugate deviation to the left side, was admitted to our clinic. The clinical symptoms were similar to an apoplexic attack. The neurologic examination showed right hyperactive knee and ankle reflexes, and left inferior temporal retinal arterial occlusion. The serial left carotid angiography, performed immediately after admission, showed the occlusion of left middle cerebral artery at the location of trifurcation. We diagnosed this case as a cerebral vascular disease, and then the large amount of Urokinase and Heparin were injected immediately after the diagnosis. The clinical symptoms were improved tremendously after the injection. Three days later, the second left carotid angiography showed the complete recanalization of the occlusion, and further did a tumor stain at the distal portion of the occlusion. The brain scintigram revealed an increased up-take of 99mTc in the left parieto-temporal region. We finally diagnosed brain tumor, and the tumor was subtotally removed by the left parieto-temporal craniotomy. The histological findings of the tumor showed angioblastic meningioma. The cerebral arterial occlusion secondary to the brain tumor should be caused by the compression of the vessels and the hemorrhage of the tumor. This case is rarely reported.
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PMID:[Middle cerebral arterial occlusion secondary to brain tumor -- case report (author's transl)]. 57 68

In summary, studies of the expression of fibrinolytic genes in the vessel wall suggest an active, ongoing proteolytic process, the activity of which is dependent on the relative amounts of tPA, uPA, and PAI-1 secreted and locally deposited. Disturbances in the balance of pro- and antifibrinolytic activity in atherosclerotic vessels have considerable potential for influencing both intra- and extravascular fibrinolytic events and may be causally related to the development of vascular disease.
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PMID:Abnormalities in the fibrinolytic system of the vascular wall associated with atherosclerosis. 753 27

Extensive beta-amyloid (A beta) deposits in brain parenchyma in the form of senile plaques and in blood vessels in the form of amyloid angiopathy are pathological hallmarks of Alzheimer's disease (AD). The mechanisms underlying A beta deposition remain unclear. Major efforts have focused on A beta production, but there is little to suggest that increased production of A beta plays a role in A beta deposition, except for rare familial forms of AD. Thus, other mechanisms must be involved in the accumulation of A beta in AD. Recent data shows that impaired clearance may play an important role in A beta accumulation in the pathogenesis of AD. This review focuses on our current knowledge of A beta-degrading enzymes, including neprilysin (NEP), endothelin-converting enzyme (ECE), insulin-degrading enzyme (IDE), angiotensin-converting enzyme (ACE), and the plasmin/uPA/tPA system as they relate to amyloid deposition in AD.
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PMID:beta-Amyloid degradation and Alzheimer's disease. 1704 8

In Alzheimer's disease (AD) Abeta accumulates because of imbalance between the production of Abeta and its removal from the brain. There is increasing evidence that in most sporadic forms of AD, the accumulation of Abeta is partly, if not in some cases solely, because of defects in its removal--mediated through a combination of diffusion along perivascular extracellular matrix, transport across vessel walls into the blood stream and enzymatic degradation. Multiple enzymes within the central nervous system (CNS) are capable of degrading Abeta. Most are produced by neurons or glia, but some are expressed in the cerebral vasculature, where reduced Abeta-degrading activity may contribute to the development of cerebral amyloid angiopathy (CAA). Neprilysin and insulin-degrading enzyme (IDE), which have been most extensively studied, are expressed both neuronally and within the vasculature. The levels of both of these enzymes are reduced in AD although the correlation with enzyme activity is still not entirely clear. Other enzymes shown capable of degrading Abetain vitro or in animal studies include plasmin; endothelin-converting enzymes ECE-1 and -2; matrix metalloproteinases MMP-2, -3 and -9; and angiotensin-converting enzyme (ACE). The levels of plasmin and plasminogen activators (uPA and tPA) and ECE-2 are reported to be reduced in AD. Reductions in neprilysin, IDE and plasmin in AD have been associated with possession of APOEepsilon4. We found no change in the level or activity of MMP-2, -3 or -9 in AD. The level and activity of ACE are increased, the level being directly related to Abeta plaque load. Up-regulation of some Abeta-degrading enzymes may initially compensate for declining activity of others, but as age, genetic factors and diseases such as hypertension and diabetes diminish the effectiveness of other Abeta-clearance pathways, reductions in the activity of particular Abeta-degrading enzymes may become critical, leading to the development of AD and CAA.
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PMID:Abeta-degrading enzymes in Alzheimer's disease. 1836 35

Thrombolytic serine proteases not only initiate fibrinolysis, but also are up-regulated in vascular disease and acute inflammatory responses. Although the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) is considered a main regulator of thrombolysis, PAI-1 is also associated with vascular inflammation. The role of other serpins that target thrombolytic proteases, PAI-2, PAI-3, and neuroserpin (NSP), in vascular inflammation is, however, less well defined. NSP is a mammalian serpin that, similar to PAI-1, inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA, respectively) and has been most closely associated with the nervous system, with a demonstrated protective role after cerebral infarction in mouse models. However, the role of NSP in systemic arterial inflammation and plaque growth is not known. Serp-1 is a myxoma viral serpin that also inhibits tPA and uPA, as well as additionally inhibiting plasmin and factor Xa (fXa). Serp-1 has proven highly potent anti-inflammatory and anti-atherogenic activity. Here we assess the effects of NSP treatment on plaque growth and T-helper (Th) lymphocyte activity in a mouse aortic allograft transplant model, with comparison to Serp-1. NSP and Serp-1 both significantly reduced plaque growth and T-cell invasion. T-bet (a Th1 differentiation marker) was significantly reduced in transplanted aorta with associated reductions in Th1 and Th17, but not Th2, in splenocytes. NSP had additional Th modifying activity in non-transplanted mice. In summary, this is the first report that NSP possesses anti-inflammatory activity in systemic arteries, modifying Th cell responses and significantly reducing plaque growth in mouse aortic allografts.
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PMID:Neuroserpin, a thrombolytic serine protease inhibitor (serpin), blocks transplant vasculopathy with associated modification of T-helper cell subsets. 2013 65

Hypertension disorders (HD) and pre-eclampsia (PRE) are leading causes of maternal deaths worldwide. PRE is associated with vascular endothelial dysfunction and with deregulation of the fibrinolysis pathway genes. Fibrinolysis is the fibrin clot hydrolysis process catalyzed by plasmin, a proteolytic enzyme formed from plasminogen. Plasminogen is cleaved by tissue-type (tPA) and urokinase-type (uPA) activators and inhibited by the plasminogen activator inhibitors type-1 (PAI-1) and type-2 (PAI-2). The whole process maintains blood hemostasis. This study aims to assess PAI-1, PAI-2, tPA and uPA mRNA expression in primary cultured human umbilical vein endothelial cells (HUVEC) isolated and cultured from healthy, HD and PRE women. Results show that PAI-1 and PAI-2 mRNA decreased in HD-HUVEC, whereas PAI-1 and uPA decreased in PRE-HUVEC cultures compared to control ones. Notably, the expression ratio between pro- and anti-fibrinolytic actors remained unchanged among the studied groups. It seems that newborn's hemostasis is maintained balanced probably by a compensatory mechanism that involves changes in the fibrinolysis gene expression profile. The real impact of these changes in mRNA expression is unknown, however, it is suggested that these changes could be associated with an increased predisposition to vascular disease development in the progeny.
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PMID:Effects of gestational hypertension and pre-eclampsia in mRNA expression of fibrinolysis genes in primary cultured human umbilical vein endothelial cells. 2979 36