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October 21, 2016





Short Description:

Subbotin proposes that blood arteries can grow diffuse tunica intimal hypertrophy(DIT) due to an unidentified stimuli, which causes hypoxia and a growth of new blood cells from the vasa vasorum, the outer cell layer.





Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target.

Topics: (click to open)

Heart Disease
Diet-Heart Hypothesis

Important Text:

Subbotin has proposed an alternate hypothesis (10, yet to be fully tested).

He proposes the fundamental event leading to the development of atherosclerosis is a triggering of proliferation (multiplication and growth) of the smooth muscle cells in the tunica intima. These are the cells in the arterial system that are known to replicate the most. Their replication can be initiated by any of a number of stimuli, including aging, transplantation, needle puncture, irradiation, hypertension, and some pharmaceutical drugs (10).

Subbotin postulates that following the triggering of their proliferation, perhaps by initiating stimuli yet to be fully understood, the mass of these cells increases. But a point will be reached at which this enlarged mass of cells can no longer remain viable without the addition of a dedicated blood supply 

Figure 6: Subbotin has proposed that the normal coronary artery may develop diffuse (tunica) intimal hypertrophy (DIT) in response to currently unidentified stimuli. The result is that the cells in the outer layer of the tunica intima, furthest from the arterial lumen and their source of oxygen, become oxygen-deficient (hypoxic). The consequence is that new blood cells grow into the intima (left side of bottom panel) from the vasa vasorum. Blood entering the intima then deposits LDL-cholesterol, which explains how lipids enter the deep layers of the intima as depicted in Figures 4 and 5. Reproduced from Figure 7 in reference 10.

When that happens, the deepest layers of the intima recruit the development of new blood vessels (neovascularization). These blood vessels arise from the vasa vasorum, which exist in the tissue layer outside the tunica media and normally provide blood (and oxygen) to the muscle cells in the tunica media of muscular arteries.

Subbotin hypothesizes that once these new blood vessels enter the deepest layers of the tunica intima, they bring with them LDL-cholesterol, which is then deposited in that cell layer, producing the changes depicted in Figures 4 and 5.

Importantly, there is substantial evidence that the vasa vasorum are intimately involved in the development of atherosclerosis, and “present data indicate that vasa vasorum neovascularisation and atherosclerosis are seemingly inseparably linked” (15, p. 878).

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