Author/Editor		Šabovič, Mišo
Title		Ateroskleroza in kardiovaskularne bolezni: (pomen "aktivne" vloge vnetja v procesu ateroskleroze)
Translated title		Atherosclerosis and cardiovascular diseases
Type		članek
Source		Farm Vestn
Vol. and No.		Letnik 54, št. Poseb št
Publication year		2003
Volume		str. 113-7
Language		slo
Abstract		The methods of modern vascular biology have allowed better understanding of mechanisms involved in the process of atherosclerosis. Currently, it is assumed that inflammation, and not lipids, plays the main and »active« role in the pathogenesis of atherosclerosis; It appears that classic risk factors primarily facilitate the inflammation in the arterial wall and secondarily directly induce atherosclerotic changes. Active role of inflammation can be divided into five consecutive processes. First process is adherence of leukocytes (monocytes and T lymphocytes) to endothelium (facilitated by adhesion molecules as VCAM-1), second process is migration of monocytes through the endothelium into intima (facilitated by chemoatractant molecules as MCP-1), and third process is activaticon of monocytes into macrophages (facilitated by activating molecules as M-CSF). Pro- inflammatory cytokines are involved in all mentioned processes. Fourth process is growing a plaque due to thrombosis occuring on surface or inside thrombi. The fifth and last process is clinically the most relevant: rupture of plaque with consequent occlusive thrombosis. Rupture is due to proteolysis of collagen in fibrous cap of plaque by metaloproteinases. Undoubtedly, further understanding of pathophysiology of atherosclerosis will allow recognition of plaques under risk of rupture and will probably help to improve treatment of atherosclerosis.
Summary		Napredek metod žilne biologije je omogočil natančnejše razumevanje patofizioloških dogajanj procesa ateroskleroze. Medtem ko so še pred leti glavno »aktivno« vlogo v procesu ateroskleroze pripisovali holesterolu, pa danes postaja vedno bolj jasno, da ima glavno »aktivno« vlogo pravzaprav vnetje. Vsi procesi, ki so vpleteni v nastanek in razpok aterosklerotičnih plakov so neposredno odvisni od vnetnih dejavnikov. Zdi se, da klasični dejavniki tveganja predvsem vplivajo na vnetje v žilni steni, v manjši meri pa tudi neposredno na sam proces ateroskleroze. Poenostavljeno lahko »aktivno« vlogo vnetja razdelimo na pet korakov. Prvi korak (vezavo monocitov na endotelij) omogočijo adhezijske molekule (VCAM-1), drugi korak (prehod monocitov v intimo) omogočijo kemotaktične molekule (MCP-1) in tretji korak (aktivacijo monocitov v makrofage) omogočijo »aktivacijske« molekule (M-CSF); (v vseh treh korakih imajo pomembno vlogo tudi pro-vnetni citokini). Četrti korak sta večanje in rast plaka kot posledica tromboz na površini ali v notranjosti plaka, ki se zacelijo z odlaganjem veziva. Zadnji in klinično najbolj usoden je peti korak (ruptura plaka) povzročen z metaloproteinazami, ki razgrajajo fibrozno kapo. Ruptura plaka povzroči akutne zaplete ateroskleroze kot je npr. srčni infarkt. Nadaljnje razumevanje pomena vnetja v procesu ateroskleroze bo omogočilo prepoznavanje plakov z velikim tveganjem za rupturo in morda vplivalo na učinkovitejše zdravljenje aterosklerotičnega procesa.
Descriptors		CARDIOVASCULAR DISEASES ENDOTHELIUM, VASCULAR INFLAMMATION INFLAMMATION MEDIATORS