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)

Neuropathological evidence of demyelination was found in the brain and sciatic nerve of diabetic patients at autopsy. The activity of acid proteinase was somewhat increased in the white matter but decreased in the gray matter of diabetic patients. No increase was observed in the activity of neutral proteinase in diabetic white and gray matter. The activities of beta-glucuronidase and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) were of the same level as those of the controls. The activities of all 4 enzymes appeared to be increased in the diabetic nerve, with the possible exception of CNP which was measured from only 1 nerve. Furthermore, the amount of total protein was markedly decreased in diabetic peripheral myelin. The encephalitogenic basic protein of diabetic brain myelin was normal in the disc gel electrophoretic patterns of brain myelin proteins. However, the basic proteins of peripheral myelin were reduced in a number of diabetic patients. The present biochemical findings for diabetic white and gray matter were largely normal. Instead, the increased activities of at least the proteinases and beta-glucuronidase in diabetic peripheral nerve, together with the loss of basic proteins, indicate extensive biochemical damage of the peripheral nervous system in diabetes. They suggest that demyelination and other phenomena observed in diabetic peripheral nerve are not caused only by angiopathy and impaired circulation.
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PMID:Enzyme and protein studies of demyelination in diabetes. 7 40

Epidemiological evidence suggests a positive correlation between the number of PMN and the risk of ischemic vascular disease. The observation that activated PMN induce platelet activation my provide some biological plausibility to the role of PMN in thrombogenesis. Between other PMN products, cathepsin G, a protease released during PMN activation, is a potent platelet agonist. However, the antiproteinases present in plasma could virtually abolish its activity. Indeed it was shown that, when PMN were stimulated after interaction with platelets in mixed cell population, P-selectin-mediated platelet-PMN adhesion may result in the formation of a sequestered microenvironment in which cathepsin G activity is protected by antiproteases. P-selectin-mediated adhesion was also shown to facilitate the transcellular metabolism of arachidonic acid, resulting in increased production of both thromboxane B2 and leukotriene C4. PMN adhesion to activated platelets in mixed cell suspensions subjected to high shear rate can be modeled as an adhesion cascade involving a P-selectin-dependent recognition step followed by an adhesion-strengthening interaction mediated by the beta(2)-integrin Mac-1. Moreover, an intermediate tyrosine-kinase-dependent signal regulating beta(2)-integrin adhesiveness is required. Indeeed activated platelets express not only P-selectin but also different beta(2)-integrin ligands including fibrinogen and ICAM-2. Some of the functional responses elicited by P-selectin on PMN could be prevented by specific antibody to the P-selectin glycoprotein ligand-1, indicating that this adhesive receptor is able to transduce an 'outside-in' signal when engaged by the ligand. By using activated platelets, P-selectin-expressing CHO cells and soluble recombinant P-selectin, P-selectin was shown to trigger protein tyrosine phosphorylation in PMN and the tyrosine kinase-dependent function of Mac-1. In conclusion, adherence of activated platelets to PMN may be a key event in the sequence of thrombus formation. The recognition of the essential contribution of PMN beta(2)-integrins in addition to P-selectin in platelet-PMN adhesion provides an additional evidence to the broad range of function and mechanisms in which PMN integrins are involved and may be potential targets for pharmacological intervention.
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PMID:Recent advances in platelet-polymorphonuclear leukocyte interaction. 1049 33

Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease critical for the activation of granule-associated serine proteases, including neutrophil elastase, cathepsin G, and proteinase 3. DPPI and granule-associated serine proteases have been shown to play a key role in regulating neutrophil recruitment at sites of inflammation. It has recently been suggested that neutrophils and neutrophil-associated proteases may also be important in the development and progression of abdominal aortic aneurysms (AAAs), a common vascular disease associated with chronic inflammation and destructive remodeling of aortic wall connective tissue. Here we show that mice with a loss-of-function mutation in DPPI are resistant to the development of elastase-induced experimental AAAs. This is in part because of diminished recruitment of neutrophils to the elastase-injured aortic wall and impaired local production of CXC-chemokine ligand (CXCL) 2. Furthermore, adoptive transfer of wild-type neutrophils is sufficient to restore susceptibility to AAAs in DPPI-deficient mice, as well as aortic wall expression of CXCL2. In addition, in vivo blockade of CXCL2 by using neutralizing antibodies directed against its cognate receptor leads to a significant reduction in aortic dilatation. These findings suggest that DPPI and/or granule-associated serine proteases are necessary for neutrophil recruitment into the diseased aorta and that these proteases act to amplify vascular wall inflammation that leads to AAAs.
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PMID:Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms. 1730 Dec 45