Fatty streaks

Kaartinen M, Penttila A, Kovanen PT Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation 1994 90 1669. Kaartinen M, Penttila A. Kovanen PT Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas. Arterioscler Thromb 1994 14 966. 

At cellular level each stage of atheroma development is accompanied by the expression of specific glycoproteins by endothelial cells which mediate the adhesion of monocytes and T-lymphocytes. Their recruitment and migration is triggered by various cytokines released by leukocytes and possibly by smooth muscle cells. Atheroma development continues with the activation of macrophages, which accumulate lipids and become, together with lymphocytes, so-called fatty streaks. The continuous influx, differentiation and proliferation finally leads to more advanced lesion and to the formation of the fibrous plaque. ... 

The earliest recognizable lesion of atherosclerosis is the fatty streak, an a egation of lipid-rich macrophages and... 

Carew, T.E., Schwenke, D.C. and Steinberg, O. (1987). Antiatherogenic effect of probucol unrelated to its hyper-cholesterolaemic effect evidence that antioxidants in vim can selectively inhibit low density lipoprotein degradation in macroph -rich fatty streaks slowing the progression of atherosclerosis in the WHHL rabbit. Proc. Natl Acad. Sci. USA 84, 7725-7729. 

It is unlikely that the damaging effects of ox-LDL are relevant only to the walls of blood vessels and there is no reason to suppose they are confined to one disease. The initial histopathologjcal sign of coronary heart disease is the appearance of the fetty streak on the luminal surfece of arteries. Fatty streaks are composed of aggregated macrophages that have taken up ox-LDL via the scavenger receptor. Recently, we have detected such foam cells in the rheumatoid synovium (Section 5.5). 

In atherosclerosis, ox-LDL is taken up ultimately by macrophages and smooth muscle cells in the arterial intima. Once loaded with lipid, these cells have a foamy appearance when examined histologically. The accumulation of these so-called foam cells in the artery wall leads to the formation of fatty streaks , which can lead to atheromatous plaque formation and consequent coronary heart disease. 

Dysfunction of the endothelium allows lipoproteins, predominantly low-density lipoprotein (LDL) cholesterol, and inflammatory cells, namely monocytes and T lymphocytes, to migrate from the plasma to the sub-endothelial space. Monocyte-derived macrophages ingest lipoproteins to form foam cells. Macrophages also secrete growth factors that promote smooth muscle cell migration from the media to the intima. A fatty streak consists of lipid-laden macrophages and smooth muscle cells and is the earliest type of atherosclerotic lesion. 

Lipid-laden macrophages, smooth muscle cells, and necrotic debris from the death of foam cells accumulate in the subendothelial space, leading to enlargement of the fatty streak. A collagen matrix forms a fibrous cap that covers the lipid core of the lesion to establish a fibrous plaque called an atherosclerotic plaque. Initially, the diameter of the coronary artery lumen is... 

Endothelial dysfunction, inflammation, and the formation of fatty streaks contribute to the formation of atherosclerotic coronary artery plaques, the underlying cause of coronary artery disease (CAD). The predominant cause of ACS, in more than 90% of patients, is atheromatous plaque rupture, Assuring, or erosion of an unstable atherosclerotic plaque that occludes less than 50% of the coronary lumen prior to the event, rather than a more stable 70% to 90% stenosis of the coronary artery.3 Stable stenoses are characteristic of stable angina. 

In Apo E-deficient animals fed a normal chow diet, fatty streaks are first observed in the proximal aorta at 10 to 12 weeks (15). The xanthoma that forms in the intima contains foam cells and is often called the early atherosclerotic lesion and is critically dependent on monocytes. Smooth muscle cells (SMCs) arrive in the intima at approximately 15 weeks and form a fibrous cap around 20 weeks (16). By 36 weeks, lumen narrowing occurs in the external branches of the carotid artery (incidence -75%), but the lumen size is maintained in the aorta. Lumen narrowing, or stenosis, does not correlate with plaque size but... 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

The formation of atherosclerotic plaques is the underlying cause of coronary artery disease (CAD) and ACS in most patients. Endothelial dysfunction leads to the formation of fatty streaks in the coronary arteries and eventually to atherosclerotic plaques. Factors responsible for development of atherosclerosis include hypertension, age, male gender, tobacco use, diabetes mellitus, obesity, and dyslipidemia. 

Elhage R, Arnal JF, Pieraggi MT, Duverger N, Fievet C, Faye JC, Bayard F (1997) 17 beta-estradiol prevents fatty streak formation in apolipoprotein E-deficient mice. Arterioscler Thromb Vase Biol 17 2679-2684... 

Navab M, Berliner JA, Watson AD, et al. (1996) The Yin and Yang of oxidation in the development of the fatty streak a review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vase Biol 16 831-842... 

HDL is synthesized in the liver and intestines and released as dense protein-rich particles into the blood. They contain apoA-1 used for cholesterol recovery from fatty streaks in the blood vessels. HDL also carry apoE and apoC-11, but those apoproteins are primarily to donate temporarily to chylomicrons and VLDL. 

As the fatty streak enlarges over time, necrotic tissue and fiee lipid accumulates, surrounded by epithelioid cells and eventually smooth muscle cells, an advanced plaque with a fibrous cap. The plaque eventually begins to occlude the blood vessel, causing ischemia and infarction in the heart, brain, or extremities. 

Even during the first or second decade of life, small deposits of lipid, fatty streaks, are often detectable in arterial walls. In a study by R. Ross over half of the children (age 10-14) examined at autopsy had fatty streaks in their arteries. These are the first indications of the entry of fat and cholesterol into macrophages in the subendothelial space of an artery. This initiates a sequence of processes that eventually produces a plaque. A prerequisite for the development of fatty streaks, and hence atherosclerosis, is injury to the endothelial cells fining the arterial wall. Many factors are suspected of causing this, including pollutants. 

Pearson, T. A., Wang, A., Solez, K. and Heptinstall, R. H Clonal Characteristics of Fibrous Plaques and Fatty Streaks from Human Aortas , Am. J. Palhol. (1975) 81, 379,... 

Cardiovascular heart diseases (CHD) are considered as the clinical expression of advanced atherosclerosis. One of the initial steps in atherogenesis is the oxidative modification of LDL and the uptake of the modified lipoprotein particles by macrophages, which in turn become lipid laden cholesterol-rich cells, so-called foam cells [159]. An accumulation of foam cells in the arterial wall is the first visible sign of atherosclerosis and is termed fatty streak, the precursor to the development of the occlusive plaque [160]. It is well known that oxidation of LDL can be initiated in vitro by incubating isolated LDL particles with cells (macrophages, lymphocytes, smooth muscle cells, or endothelial cells), metal ions (copper or iron), enzymes, oxygen radicals, or UV-light. However less is known about the mechanisms by which... 

The two significant sources of cholesterol in body are endogenously synthesized cholesterol and exogenous or dietary cholesterol. Efforts to inhibit the absorption of dietary cholesterol have primarily focused on the inhibition of ACAT, a major enzyme associated with cholesterol esterification. Inhibition of this enzyme blocks the absorption of intestinal cholesterol and may also inhibit cholesteryl ester deposition in the vascular wall in the form of fatty streaks associated with atherosclerotic plaque. 

Auger C, Teissedre PL, Gerain P, Lequeux N, Bomet A, Serisier S, Besancon P, Caporiccio B, Cristol JP, Rouanet JM. 2005. Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem 53 2015-2021. 

The atherosclerotic lesions develop in a complex, chronic process. The first detectable lesion is the so-called fatty streak, an aggregation of lipid-laden macrophage foam cells. The next stage of development is the formation of plaques consisting of a core of lipid and necrotic cell debris covered by a layer of connective tissue and smooth muscle cells. These plaques hinder arterial blood flow and may precipitate clinical events by plaque rupture and thrombus formation. Platelets from the thrombi, activated macrophages, and smooth muscle cells release growth factors and cytokines resulting in an inflammatory-fibroproliferative response that leads to the advanced lesions of atherosclerosis. 

Similar trends were observed in ovariectomized Syrian hamsters (Lucas et al., 2004). Flaxseed diets of 7.5%, 15%, or 22.5% for 120 days were able to prevent the rise in plasma cholesterol that was observed in the ovariectomized hamsters. Nearly 61% of the aorta contained fatty streaks in the ovariectomized hamsters, whereas the ovariectomized hamsters on the 7.5% and 22.5% flaxseed diets had aortic fatty streaks over 7.5% and 7.2% of the aorta, respectively (Lucas et al., 2004). This difference was nearly an 88% reduction in atherosclerosis compared to ovariectomized hamsters. 

---