Kamis, 26 Januari 2012

CHOLESTEROL 11 - Atherosclerosis 7


Daftar Jamu Godog Kendhil Kencana >>>Jamu Godog Penurun Cholesterol – LEMAK NORMAL

The thrombotic complications of atherosclerosis. 
Thrombi complicating atheroma arise by 2 major mechanisms. 
The first, depicted in the left panel of this diagram, involves a through-and-through rupture of the plaque’s fibrous cap, 
which has been weakened by the mechanisms described in the text and in the legend to Figure 3. 
The rent in the fibrous cap permits blood and its coagulation factors to contact tissue factor expressed by macrophages 
and smooth muscle cell (SMC) and on microparticles elaborated by these cells and endothelial cells (EC). 
Moreover, the activated cells in the local environment of the plaque, including ECs and SMCs, 
elaborate large amounts of plasminogen activator inhibitor-1, 
a potent inhibitor of the endogenous fibrinolytic enzymes also found in the plaque such as urokinase and tissue-type plasminogen activator. 
A second common mechanism of coronary thrombus formation involves a superficial erosion of the endothelial cells (right panel), 
perhaps caused by endothelial apoptosis or desquamation.
Potential molecular imaging targets in atherosclerosis. 
White boxes show putative targets for molecular imaging of atherosclerosis. Atherogenesis involves recruitment of inflammatory cells from blood, 
represented by the monocyte in the upper-left-hand corner of this diagram. 
Monocytes are the most numerous leukocytes in atherosclerotic plaque. 
Recruitment depends on expression of adhesion molecules on macrovascular endothelium, as shown, and on plaque microvessels. 
Once resident in the arterial intima, activated macrophages become phagocytically active, a process that provides another potential target for plaque imaging. 
Oxidatively modified low-density lipoprotein (mLDL)–associated epitopes that accumulate in plaques may also serve as targets for molecular imaging. 
Foam cells may exhibit increased metabolic activity, augmenting their uptake of glucose, a process already measurable in the clinic by 18F-FDG uptake. 
Activated phagocytes can also elaborate protein-degrading enzymes that can catabolize collagen in the plaque's fibrous cap, 
weakening it, and rendering it susceptible to rupture and hence thrombosis. 
Mononuclear phagocytes dying by apoptosis in plaques display augmented levels of phosphatidylserine on their surface. 
Probes for apoptosis such as annexin V may also visualize complicated atheromata. 
Microvessels themselves can express not only leukocyte adhesion molecules (shown in green) but also integrins such as αVβ3. 
Proof-of-principle experiments in animals support each process or molecule in white boxes as target for molecular imaging agents.
ERα, ERβ, and gpER: novel aspects of oestrogen receptor signalling in atherosclerosis.
Molecular targets of oestrogens in the normal (left) and atherosclerotic vascular wall (right). 
With the progression of an atherosclerotic lesion as well as with ageing, 
expression of ERα and ERβ becomes a target of methylation (CH3)-associated inactivation. 
Moreover, expression of oestrogen receptor-associated co-regulatory proteins, such as NM23-H2, is altered, 
and ERβ expression changes in advanced atherosclerosis. 
Local formation of biologically active oestrogens through aromatase and other pathways appears to be reduced (E2 ↓) under these conditions. 
Based on these changes of oestrogen receptor signalling in advanced atherosclerosis, 
it is currently not clear how endogenous oestrogens affect oestrogen-dependent proteins involved in inflammation and structure of the atherosclerotic plaque, such as inflammatory nitric oxide synthase (iNOS) and matrix metalloproteinases (MMP). 
This illustrates the complexity of action of oestrogens and how equine oestrogen mixtures containing hormonal substances of unidentified activity affect oestrogen receptor function and regulation of oestrogen-sensitive genes in the presence of atherosclerosis. gpER, G protein-coupled estrogen receptor.

Daftar Jamu Godog Kendhil Kencana >>>Jamu Godog Penurun Cholesterol – LEMAK NORMAL

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