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May 27, 2007

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Nakashima publishes a study that shows the early stages of coronary atherosclerosis in which the initial fat deposition occurs in the deep layers of the tunica intima, which are separated from the subendothelial region by numerous cell layers and matrix





Early human atherosclerosis. Accumulation of lipid and proteoglycans in intimal thickenings followed b macrophage infiltration.


Important Text:

The second critical finding reported by Nakashima and colleagues already in 2007 (13) and essentially forgotten until its rediscovery by Subbotin (10, 11) is the initial deposition of lipid material in the walls of arteries affected by atherosclerosis. This occurs in the deep layers of the tunica intima. These layers are separated from the endothelial cell layer by numerous layers of smooth muscle cells (Figure 4).

Figure 4: The panels on the left (panels a, d, and g) show the histological evolution of the fatty streaks in arteries of different subjects dying from different causes. The middle panels (b, e, and h) show the site at which lipid (staining red) begins to accumulate. Note especially in panel h that the main site of accumulation is in the deep layers of the tunica intima, close to the internal elastic lamina. The panels on the right (panels c, f, and i) are stained to detect the presence of macrophages. The panels show that despite some degree of lipid accumulation (panels e and h), there is no evidence for the invasion of macrophages. Figures 1 and 2 require that an invasion by macrophages into the (non-existent) subendothelial space is essential for the development of atherosclerosis. Reproduced from Figure 6 in reference 10.

The point of Figure 4 is to show that since the first evidence for lipid accumulation in diseased arteries occurs so deep in the tunica intima, it cannot have arisen from the LDL-cholesterol carried in the lumen of the arteries. There has to be another source for this lipid accumulation.

doi: 10.1161/ATVBAHA.106.134080. Epub 2007 Feb 15.. 2007 May;27(5):1159-65.Arterioscler Thromb Vasc Biol

Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration

Yutaka Nakashima 1Hiroshi FujiiShinji SumiyoshiThomas N WightKatsuo Sueishi

Affiliations expand


Objective: The present study was designed to clarify the morphological features of early human atherosclerosis and to determine whether specific extracellular matrix proteoglycans play a role in early atherogenesis.

Methods and results: Step and serial sections were obtained from right coronary arteries with no or early atherosclerosis. Atherosclerosis was classified into 4 grades according to the amount of lipid deposition. Coronary arteries with Grade 0 showed diffuse intimal thickening (DIT) with no lipid deposits. The extracellular matrix proteoglycans, biglycan and decorin, were localized in the outer layer of DIT. Most cases of Grade 1 and Grade 2 exhibited fatty streaks with extracellular lipids colocalizing with biglycan and decorin in the outer layer of the intima. As lipid grades increased, macrophages increased in number and were present in the deeper layers. Most cases of Grade 3 exhibited pathologic intimal thickening (PIT) with extracellular lipids underneath a layer of foam cell macrophages.

Conclusions: In early human coronary atherosclerosis, fatty streaks develop via extracellular deposition of lipids associated with specific types of proteoglycans in the outer layer of preexisting DIT. As the amount of the lipid increases in fatty streaks, macrophages infiltrate toward the deposited lipid to form PIT with foam cells.

Topics: (click image to open)

Heart Disease
Heart disease, also known as cardiovascular disease, refers to a range of conditions that affect the heart and blood vessels. It is a broad term that encompasses various conditions, including coronary artery disease, heart failure, arrhythmias, and valvular heart diseases, among others. Heart disease is a leading cause of death worldwide.
Diet-Heart Hypothesis
The diet-heart hypothesis, also known as the lipid hypothesis, proposes that there is a direct relationship between dietary fat intake, particularly saturated fat and cholesterol, and the development of heart disease. It suggests that consuming high amounts of these fats leads to an increase in blood cholesterol levels, specifically low-density lipoprotein (LDL) cholesterol, which in turn contributes to the formation of atherosclerotic plaques in the arteries. Some consider this hypothesis nothing more than wishful thinking.
Cholesterol is an animal based molecule that forms cell membranes. It's a lipid known as a sterol. Cholesterol is found in all animal foods and is healthy to eat, despite the opinions set forth by the diet-heart hypothesis. Lipoproteins carry cholesterol as well as other lipids.
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