The blood vessels of the body are lined with what are called endothelial cells. One of the primary functions of these cells is to maintain the canals that deliver nutrients to the tissues of the body. In recent cardiovascular research, the link between atherosclerosis (hardening of the arteries) and the health of the endothelial cells has become increasingly clear. For a scientific review of the recent research, click here. "Nitric oxide pathway as new drug targets for refractory hypertension." Curr Pharm Des. 2005;11(25):3307-15. This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

By Benjamin V. Treadwell, Ph.D.

You do the right thing by making a yearly office visit to your healthcare professional, and you try to heed his/her advice. But often you’re not sure, since there is so much conflicting information out there. This lack of conviction is at least partly due to the fact that it is difficult for health professionals to keep up to date with the rapidly evolving medical science that underlies the advice.

New discoveries are helping to change this picture. For example, we are told that a high cholesterol level is dangerous. Why?

Why is elevated blood-cholesterol bad?

Lots of evidence points to elevated blood levels of cholesterol as a cause of atherosclerosis (hardening of the arteries). However, the connection between high cholesterol and disease is complex. Most of our cholesterol is synthesized in the liver and subsequently combines with additional cellular constituents, such as lipids and proteins, before being released into the bloodstream. It turns out that a number of different molecules associate with cholesterol, and the type of cholesterol-associated molecules determines the size and density of the final structure, and therefore the type of cholesterol.

For example, several different types of cholesterol-associated, blood-borne structures differ from one another with respect to their size and density. These differences are partially the consequence of the ratio of fat to protein in the particle, as well as to the specific type of fat-carrying proteins, lipoproteins, which help sort and pack the fats to give the final shape, size, and density to the cholesterol-laden particle. This is the reason our cholesterol test results contain the designations HDL, LDL, and sometimes VLDL, for high density lipoprotein cholesterol, low density lipoprotein cholesterol, and very low density lipoprotein cholesterol. Let’s take a look at the two most studied cholesterols, HDL and LDL.

Why LDL is the "Lousy" cholesterol?

LDL is the particle responsible for delivering cholesterol to cells where it is converted to important substances such as hormones. We need a certain amount of it for maximum health. The problem arises when we have too much. LDL, because of its structure, is easily oxidized to form oxLDL – especially under conditions of high oxidant stress (unfavorable oxidant/antioxidant ratio).

		How Much Cholesterol? The American Heart Association recommends:  •  Total cholesterol level of less than 200 mg/dL  •  LDL less than 100 mg/dL  •  HDL greater than 60 mg/dL

oxLDL has been shown to bind to specific sites on endothelial cells, which line the walls of blood vessels. These cells are responsible for maintaining the health of our arteries. One effect of oxLDL is to impair the activity of the endothelial cell enzyme nitric oxide synthase (eNOS). This enzyme is responsible for producing the vascular relaxing factor, nitric oxide, which in turn helps keep proper vascular tone and blood pressure. When the enzyme is impaired by interaction with oxLDL, nitrous oxide (NO) production decreases, causing the vessel to constrict, blood pressure to rise, and inflammatory cells to move into the area surrounding the cell-bound oxLDL. In fact, recent evidence associates low levels of NO with increased production of oxLDL. So it’s kind of a vicious cycle: oxLDL decreases the production of NO, and this in turn promotes endothelial cell dysfunction and increased inflammation, oxidant stress and more oxLDL production. The impairment of endothelial cell function is believed by some to be one of the initial events promoting the buildup of plaque in arteries and progressing to atherosclerosis.

Factors that promote the oxidation of LDL include elevated blood levels of LDL, hypertension (high blood pressure), increased stress (both physical and emotional), and an imbalance in the oxidant/antioxidant ratio in the cell and cellular environment, in favor of oxidants. Once the atherosclerotic process is initiated, inflammatory cells and chemical messengers move into the interior of the artery wall and rev-up the machinery involved in oxidant production. This process leads to a series of scarring-healing events within the arterial wall, resulting in a gradual closing of the artery and finally complete blockage.

What makes HDL the healthy cholesterol?

This is the interesting part of the story. HDL does lots of good things. It has the remarkable effect of improving endothelial function, by at least two mechanisms. It lowers levels of LDL by picking up cholesterol from cellular LDL and transporting cholesterol back to the liver, where it is processed and excreted as a component of bile. Furthermore, it improves the health of vascular endothelial cells lining the arteries by stimulating the activity of eNOS. Increased activity of this enzyme stimulates the production of NO, and hence a reduction in vascular constriction, and blood pressure. This too helps lower the oxidant stress placed on the endothelial cell.

Summary: The endothelial cells that line the walls of the arteries are the regulators of vascular tone and health of the artery. A key mechanism involved in regulating vascular health involves the eNOS-NO pathway. Thus, endothelial cell dysfunction is the consequence of faulty or impaired synthesis of NO by a defective endothelial cell eNOS enzyme. Oxidant stress can exacerbate this condition, and HDL can improve it.

Things to do to increase HDL and lower LDL

Prescription cholesterol-lowering drugs are effective in decreasing total cholesterol, but many are not as effective with regard to increasing the levels of healthy cholesterol or improving the HDL to LDL ratio. The B vitamin niacin, prescribed in combination with the common cholesterol-lowering drugs, does have a significant effect on lowering LDL and raising HDL. Lifestyle, exercise and diet are important factors too in improving endothelial health. Recent evidence also suggests that some antioxidants may have a role in helping to prevent vascular disease by protecting the endothelial cell as well as its product, NO.