Transcript Emostasi e trombofilia

A
Maria Antonietta Lepore
Emostasi e trombofilia
Polimorfismi genetici associati alle patologie
cardiovascolari e neurodegenerative
Aracne editrice
www.aracneeditrice.it
[email protected]
Copyright © MMXVI
Gioacchino Onorati editore S.r.l. – unipersonale
www.gioacchinoonoratieditore.it
[email protected]
via Sotto le mura, 
 Canterano (RM)
() 
 ----
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I edizione: dicembre 
Indice
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Abstract
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Forward
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Introduzione
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Capitolo I
Principali fattori della coagulazione
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Capitolo II
Ruolo della trombina nella formazione del coagulo
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Capitolo III
Polimorfismi genetici associati al rischio di eventi di
malattie cardiovascolari
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Capitolo IV
Rischio cardiovascolare residuo
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Capitolo V
Metabolismo dell’omocisteina
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Capitolo VI
Trattamento delle malattie neurodegenerative
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Conclusioni
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Bibliografia
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Abstract
LDL cholesterol (LDL–C) has been the cornerstone measurement for assessing cardiovascular risk for nearly 
years. Recent data demonstrate that apolipoprotein B (Apo–
B) is a better measure of circulating LDL and the concentration is a more reliable indicator of risk than LDL–C. In
this report, we review the studies of apo B and LDL–C
reported to date, discuss potential advantages of their measurement over that of LDL–C and the present information
related to standardization.
In line with recently guidelines, the addition of apo B
represents a next most important step.
Thus, it appears to consider using apo B along with
LDL. C to asses LDL related risk for an period until the
superiority of apo B is generally recognized.
Recent genome–mitochondrialDNA association studies have pinpointed many loci associated with neurovegetative disease’s.
We have studied the association between genetic mutation factors on a whole mtDNA in longitudinal study
design has enabled the investigation of genetic variation
influencing trait values over time.
Keywords: Thrombin. LDL–Cholesterol, Apolipoprotein
B–, Oligonucleotides, Mitochondria, Neurodegenerative disease.
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Forward
The serine protease thrombin plays an important role in
a variety of biological events, including blood coagulation,
cell proliferation, and inhibition of neurite outgrowth. This
activities makes thrombin both an model for studyng the
structure–function relationships of serine proteases and a
primary target for the design od antithrombotic drugs.
One of the unique features of thrombin structure is the
presence of many basic aminoacid residues within surface loops, especially in a region called the anion–binding
exosite. These positively charged residues contribute significantly to the specificity of thrombin activity. In fact, the
basic amino acids in the anion–binding exosite are major
determinants for the interactions with fibrinogen, thrombomodulin, the platelet thrombin receptor, and heparin
cofactor. The binding sites for thrombin on most of these
substrates, cofactors, and inhibitors are frequently located
in regions rich in acidic amino acids, which are probably
involved in ionic interaction with the thrombin exosite.
This work suggest that the single stranded DNA binding
site is located in the thrombin anion–binding exosite and
overlaps with the binding sites for fibrinogen, the platelet thrombin receptor, and thrombomodulin. In previous studies,
site–directed mutagenesis of thrombin had comparable effects on fibrinogen clotting and platelet activating activities. This
correlation indicates that the sites on thrombin for fibrinogen
and platelet thrombin receptors are similar.
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Forward
Activation of protein C is an important anticoagulant
activity of thrombin and this reaction is dramatically stimulated by thrombomodulin, an endothelial cell surface
glycoprotein. Structural determinants for interaction with thrombomodulin are localized in the anion binding
exosite of thrombin.
In the absence of thrombomodulin, protein C activation
is markedly inhibited by calcium ions but proceeds at a
significant rate in the presence of EDTA.
Platelet aggregation was followed by the increase in
light transmission.
In hemostasis, thrombin has both procoagulant and
anticoagulant activities. Thrombin converts fibrinogen to
fibrin, and activates platelets and coagulation factors V, VIII,
XI, XI, XIII. Thrombin also activates anticoagulant protein
Cby a thrombomodulin dependent mechanism. The regulation of thrombin functions is extremely important to the
pathophysiology and treatment of thrombotic disorders.
Since both single and double stranded DNA molecules
as well as RNA molecules can be selected for specific
ligand binding in vitro, this approach also provides a new
strategy for the design of a variety of protease inhibitors.
The anion binding exosite is an important determinant for thrombin recognition of substrates, cofactors and
inhibitors.
Keywords: Thrombin, oligonucleotides, LDLCholesterol,
Apoprotein B–, mitochondrial–DNA, neurovegetative
diseases.
Introduzione
L’emostasi, in condizioni fisiologiche, rappresenta il meccanismo attraverso cui si realizza l’impedimento o l’arresto
del sanguinamento.
Infatti, se un vaso viene leso con interruzione della continuità del fluido ematico nel torrente circolatorio, inizia
una serie a catena di eventi che porta ad un arresto della
fuoriuscita di sangue. Quando un vaso sanguigno viene
leso, l’emostasi viene attivata attraverso alcuni meccanismi, quali lo spasmo vascolare, la formazione di un tappo piastrinico, la coagulazione del sangue per tamponare
l’emorragia e chiudere il vaso reciso.
Può essere fisiologica, emostasi spontanea, causata dalla
vasocostrizione, oppure determinata dai farmaci coagulanti e/ o procedimenti meccanici.
Lo spasmo vascolare si verifica quando un vaso sanguigno viene reciso ed è determinato dal trauma vascolare
quando la sua parete si contrae. Quanto maggiore è il
trauma subito dal vaso, tanto più grande è lo spasmo.
La vasocostrizione è efficace nel ridurre l’entità dell’emorragia.
In questo complesso processo fisiologico gioca un ruolo predominante il fibrinogeno, che per azione dell’enzima proteolitico trombina, viene trasformato in fibrina,
prodotto finale della coagulazione. L’unione dei tre elementi fibrina–cellule ematiche–piastrine forma un tappo
che arresta la fuoriuscita del sangue dal vaso reciso.
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