Aterogeneza: značaj lipidskih poremećaja i

oksidativnog stresa.

Novi faktori rizika za ishemijsku bolest srca

Doc. Dr Zvezdana Kojić

Decembar 2004.

Biološki mehanizmi regulacija- Fiziologija kardiovaskularnog sistema -

Atherosclerosis:a multifactorial disease

Arterial wall:structure and function

Different stages of atherosclerotic plaquedevelopment

Vascular endothelium modificationin atherosclerosis

Plaque formation

1 — Fatty streak

Plaque formation

2 — Fibrous cap

Plaque formation

3 — Lipid core

Lipid core constitutionActivated macrophages accumulate lipids

Lipid core constitutionLDL oxidation

Parietal vascular inflammationThe activated macrophage produces

inflammatory cytokines

From plaque to thrombosis, key event: plaque rupture

Plaque vulnerability

Key role of macrophages

Vulnerable plaqueKey role of the macrophage in vascular wall inflammation

Fibrinogen is an independent risk factorfor atherosclerosis

Vulnerable plaqueKey role of the macrophage in the degradation

of the fibrous cap

Tissue factor: the initiator of coagulation and thrombogenesis in vivo

Tobacco and atherosclerosis

Dyslipidemia and atherosclerosis

Novi faktori rizika

• ADMA ?

• homocistein

• grelin, leptin

• mokraćna kiselina

• Mg++, Fe++, Zn++, Cu++

Literatura

• Li AS., Glass CK. PPAR and LXR-dependent pathways controlling lipid metabolism and development of atherosclerosis. J Lip Res., 2004, 45(12): 2161-73.

• Francois M, Kojda G. Effect of hypercholesterolemia and of oxidative stress on the nitric oxide-cGMP pathway. Neurochem Int. 2004 Nov;45(6):955-61.

• Bursill CA, Choudhury RP, Ali Z, Greaves DR, Channon KM. Broad-spectrum CC-chemokine blockade by gene transfer inhibits macrophage recruitment and atherosclerotic plaque formation in apolipoprotein E-knockout mice. Circulation, 2004, 110(16): 2460-6.