The term atherosclerosis is prorposto by Marchand in 1904 to highlight the presence of ' atheroma (from the greek ather, which means "jelly" to indicate the fatty material, poltaceo contained in the plaques). Lesions evolve over time: starting in childhood as fatty streaks (purely reversible) and tend to become true atherosclerotic plaques, which in advanced stages can narrow (stenosis), the arterial lumen or ulcer and complicated by a superimposed thrombosis, which can lead to artery blockage. For
atherosclerosis s’intende invece un indurimento (sclerosi) della parete arteriosa che compare con il progredire dell’età.
La lesione caratteristica dell’ aterosclerosi è l’ ateroma o placca aterosclerotica , ossia un ispessimento dell’ intima (lo strato più interno delle arterie, che è rivestito dall’endotelio ed è in diretto contatto con il sangue) delle arterie dovuto principalmente all’accumulo di materiale lipidico (grasso) e a proliferazione del tessuto connettivo.
Clinicamente l’aterosclerosi può essere asintomatica oppure manifestarsi, di solito dai 40-50 anni in su, con fenomeni ischemici acuti o cronici , che colpiscono principalmente cuore, encefalo, arti inferiori e intestino.
Si tratta di una lesione imfiammatoria, ricca di macrofagi e linfociti T, preceduta da una infiltrazione nell’intima di lipoproteine a bassa densità (LDL).
La patogenesi dell’aterosclerosi e della trombosi può essere spiegata in gran parte da una triade che coinvolge la disfunzione delle cellule endoteliali , l’attivazione e l’aggregazione delle piastrine e l’intervento dei fattori della coagulazione , come il fibrinogeno. I principali Risk factors that may trigger these processes are represented dall'ipercolesterolemia, increased LDL, reduced HDL cholesterol, smoking, diabetes, high blood pressure.
L ' endothelium is a dynamic and active tissue, involved in the control of vascular function. In fact actively regulates vascular tone and permeability, the balance between coagulation and fibrinolysis, the composition of the subendothelial matrix, adhesion and transmigration of leukocytes within the vessel wall, inflammatory activity of the vessel wall and cell function vascular smooth.
Endothelial cells produce extracellular matrix components and various chemical mediators involved in the processes of vascular homeostasis, such as nitric oxide (NO), prostanoids, endothelin, angiotensin II, tissue plasminogen activator (PAI -I), Von Willebrand factor and various adhesion molecules and cytokines.
Under normal conditions the endothelium is able to: determine an active reduction in vascular tone, leukocyte adhesion limit and therefore the inflammatory activity in the vessel wall, regulate vascular permeability selective, inhibiting the adhesion producing platelet aggregation prostacyclin, NO and other things, restrict the activation of coagulation.
A particularly important endothelial mediator is radical nitric oxide (NO) which, together with prostacyclin, bradykinin and to hyperpolarizing factors, is the primary relaxing factor of vascular tone, while the factors are endothelial vasoconstrictor endothelin -I, thromboxane, activation of angiotensin II. The multiple effects of NO on the Cardiovascular system are: growth inhibition of the vascular wall and proliferation of smooth muscle cells, platelets adhesion and aggregation, the accession of monocytes to endothelial cells and release of endothelin-I.
biochemical stimuli, inflammatory and hemodynamic, as turbulent flow, can determine the different mechanisms of endothelial cell activation, which results in excessive production of adhesion molecules. The activation may be transient, if the stimuli are equally transient in time.
In contrast stimuli lead to chronic persistent alterations in endothelial function, which plays a vital role not only in the genesis of atherosclerosis, but also in the progression of the disease and sequelae.
events initials in the formation of atherosclerosis are characterized by endothelial damage (functional damage or endothelial dysfunction) and the accumulation and modification bssa density lipoprotein (LDL) in the intima of the arteries.
The accumulation of LDL due to increased permeability of the endothelium is damaged. Another factor that causes intimal thickening is represented by the friction of the bloodstream SURFACE-vascular (haemodynamic stress) which is particularly high at dele branches and curvatures of the vessels that are especially prone to the development of atherosclerotic lesions.
La disfunzione dell’endotelio ad opera dei fattori di rischio cardiovascolari, è seguita dall’adesione migrazione di monociti e linfociti T nell’intima grazie alle molecole di adesione prodotte dall’endotelio danneggiato o attivato.
I macrofagi fagocitano le lipoproteine infiltrate e si trasformano nelle cellule schiumose che caratterizzano le strie lipidiche. La secrezione di fattori di crescita da parte dei macrofagi induce la migrazione delle cellule muscolari lisce dalla media nell’intima dove proliferano determinando la trasformazione delle cellule schiumose nelle lesioni avanzate.
Alla crescita delle lesioni può contribuire l’adesione di piastrine nell’intima denudata e il formarsi di trombi intramurali, conseguenti alla erosione/ulcerazione delle placche aterosclerotiche .
Quindi nella patogenesi dell’aterosclerosi intervengono l’endotelio, i leucociti, le cellule muscolari lisce, le piastrine e rivestono un ruolo fondamentale l’infiltrazione lipidica della parete arteriosa e l’azione meccanica del flusso sanguigno sulle pareti dell’arteria.
Un evento precoce dell’aterogenesi functional endothelium is formed by the alteration of risk factors (smoking, cholesterol, high blood pressure, etc.).. The functional impairment is manifested by the expression of adhesive molecules on the cell surface and secretion of active substances that are responsible for the accession of leukocytes, but also to alterations of the haemostatic properties of the endothelium, the permeability to plasma proteins and control of vascular tone.
The fundamental role in the development of chronic inflammatory reaction is carried out by intimate oxidation of LDL, which remain trapped in the extracellular matrix subendothelial space.
oxidized LDL have a direct toxic action and stimulate the proliferation of smooth muscle cells, macrophages, fibroblasts and endothelial cells. Endothelium also stimulate the expression of adhesive molecules for leukocytes. Promote the synthesis of growth factors for monocytes / macrophages, stimulate clotting and inhibit NO production.
The clinical manifestations of atherosclerosis usually appear after the age of forty and fifty years of age and are due to ischemia (decreased blood flow) caused by arterial lumen narrowing dle.
The chronic manifestations are the result of a narrowing artery affected stable, which makes the blood flow fixed, that is unable to increase when the operating conditions require, such as during physical exertion. Consequently, the symptoms, especially pain, tends to be absent at rest and during exercise occur more or less intense, depending on the severity of hypertension. Typical syndromes are: angina pectoris, angina abdominis, intermittent claudication, in which the pain occurs during walking and usually disappears after a few minutes rest.
The acute events are the result of a sudden riduzione del lume arterioso, che provoca una brusca riduzione del flusso ematico nel territorio dipendente. In genere l’occlusione arteriosa è causata dalla rottura di una placca aterosclerotica, con conseguente trmbosi in corrispondenza della ulcerazione. Sono sindromi ischemiche acute: angina pectoris instabile, infarto miocardico, infarto intestinale, ictus ischemico.
Si tratta di una lesione imfiammatoria, ricca di macrofagi e linfociti T, preceduta da una infiltrazione nell’intima di lipoproteine a bassa densità (LDL).
La patogenesi dell’aterosclerosi e della trombosi può essere spiegata in gran parte da una triade che coinvolge la disfunzione delle cellule endoteliali , l’attivazione e l’aggregazione delle piastrine e l’intervento dei fattori della coagulazione , come il fibrinogeno. I principali Risk factors that may trigger these processes are represented dall'ipercolesterolemia, increased LDL, reduced HDL cholesterol, smoking, diabetes, high blood pressure.
L ' endothelium is a dynamic and active tissue, involved in the control of vascular function. In fact actively regulates vascular tone and permeability, the balance between coagulation and fibrinolysis, the composition of the subendothelial matrix, adhesion and transmigration of leukocytes within the vessel wall, inflammatory activity of the vessel wall and cell function vascular smooth.
Endothelial cells produce extracellular matrix components and various chemical mediators involved in the processes of vascular homeostasis, such as nitric oxide (NO), prostanoids, endothelin, angiotensin II, tissue plasminogen activator (PAI -I), Von Willebrand factor and various adhesion molecules and cytokines.
Under normal conditions the endothelium is able to: determine an active reduction in vascular tone, leukocyte adhesion limit and therefore the inflammatory activity in the vessel wall, regulate vascular permeability selective, inhibiting the adhesion producing platelet aggregation prostacyclin, NO and other things, restrict the activation of coagulation.
A particularly important endothelial mediator is radical nitric oxide (NO) which, together with prostacyclin, bradykinin and to hyperpolarizing factors, is the primary relaxing factor of vascular tone, while the factors are endothelial vasoconstrictor endothelin -I, thromboxane, activation of angiotensin II. The multiple effects of NO on the Cardiovascular system are: growth inhibition of the vascular wall and proliferation of smooth muscle cells, platelets adhesion and aggregation, the accession of monocytes to endothelial cells and release of endothelin-I.
biochemical stimuli, inflammatory and hemodynamic, as turbulent flow, can determine the different mechanisms of endothelial cell activation, which results in excessive production of adhesion molecules. The activation may be transient, if the stimuli are equally transient in time.
In contrast stimuli lead to chronic persistent alterations in endothelial function, which plays a vital role not only in the genesis of atherosclerosis, but also in the progression of the disease and sequelae.
events initials in the formation of atherosclerosis are characterized by endothelial damage (functional damage or endothelial dysfunction) and the accumulation and modification bssa density lipoprotein (LDL) in the intima of the arteries.
The accumulation of LDL due to increased permeability of the endothelium is damaged. Another factor that causes intimal thickening is represented by the friction of the bloodstream SURFACE-vascular (haemodynamic stress) which is particularly high at dele branches and curvatures of the vessels that are especially prone to the development of atherosclerotic lesions.
La disfunzione dell’endotelio ad opera dei fattori di rischio cardiovascolari, è seguita dall’adesione migrazione di monociti e linfociti T nell’intima grazie alle molecole di adesione prodotte dall’endotelio danneggiato o attivato.
I macrofagi fagocitano le lipoproteine infiltrate e si trasformano nelle cellule schiumose che caratterizzano le strie lipidiche. La secrezione di fattori di crescita da parte dei macrofagi induce la migrazione delle cellule muscolari lisce dalla media nell’intima dove proliferano determinando la trasformazione delle cellule schiumose nelle lesioni avanzate.
Alla crescita delle lesioni può contribuire l’adesione di piastrine nell’intima denudata e il formarsi di trombi intramurali, conseguenti alla erosione/ulcerazione delle placche aterosclerotiche .
Quindi nella patogenesi dell’aterosclerosi intervengono l’endotelio, i leucociti, le cellule muscolari lisce, le piastrine e rivestono un ruolo fondamentale l’infiltrazione lipidica della parete arteriosa e l’azione meccanica del flusso sanguigno sulle pareti dell’arteria.
Un evento precoce dell’aterogenesi functional endothelium is formed by the alteration of risk factors (smoking, cholesterol, high blood pressure, etc.).. The functional impairment is manifested by the expression of adhesive molecules on the cell surface and secretion of active substances that are responsible for the accession of leukocytes, but also to alterations of the haemostatic properties of the endothelium, the permeability to plasma proteins and control of vascular tone.
The fundamental role in the development of chronic inflammatory reaction is carried out by intimate oxidation of LDL, which remain trapped in the extracellular matrix subendothelial space.
oxidized LDL have a direct toxic action and stimulate the proliferation of smooth muscle cells, macrophages, fibroblasts and endothelial cells. Endothelium also stimulate the expression of adhesive molecules for leukocytes. Promote the synthesis of growth factors for monocytes / macrophages, stimulate clotting and inhibit NO production.
The clinical manifestations of atherosclerosis usually appear after the age of forty and fifty years of age and are due to ischemia (decreased blood flow) caused by arterial lumen narrowing dle.
The chronic manifestations are the result of a narrowing artery affected stable, which makes the blood flow fixed, that is unable to increase when the operating conditions require, such as during physical exertion. Consequently, the symptoms, especially pain, tends to be absent at rest and during exercise occur more or less intense, depending on the severity of hypertension. Typical syndromes are: angina pectoris, angina abdominis, intermittent claudication, in which the pain occurs during walking and usually disappears after a few minutes rest.
The acute events are the result of a sudden riduzione del lume arterioso, che provoca una brusca riduzione del flusso ematico nel territorio dipendente. In genere l’occlusione arteriosa è causata dalla rottura di una placca aterosclerotica, con conseguente trmbosi in corrispondenza della ulcerazione. Sono sindromi ischemiche acute: angina pectoris instabile, infarto miocardico, infarto intestinale, ictus ischemico.
