DEFINITION:

Atherogenesis:

The process of forming atheromas, plaques in the inner lining (the intima) of arteries.

The process of atherogenesis--cellular and molecular interaction: from experimental animal models to humans.

Atherogenesis is a disorder of the artery wall that involves: adhesion of monocytes and lymphocytes to the endothelial cell surface; migration of monocytes into the sub-endothelial space and differentiation into macrophages; ingestion of low density lipoproteins and modified or oxidised low density lipoproteins by macrophages by several pathways, including a scavenger pathway, leading to accumulation of cholesterol esters and formation of "foam cells". These foam cells together with T lymphocytes form the fatty streak.

Vascular smooth muscle cells migrate from the media into the intima and proliferate with the formation of atherosclerotic plaques. These processes which involve cell adhesion, migration, differentiation, proliferation and cell interaction with the extracellular matrix are regulated by a complex network/cascade of cytokines and growth regulatory peptides. Thus, atherosclerosis may be the result of a specialised chronic inflammatory fibroproliferative process which has become excessive and in its excess this protective response has become the disease state.

ATHEROSCLEROSIS:

Atherosclerosis is the condition in which an artery wall thickens as the result of a build-up of fatty materials such as cholesterol. It is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by low density (especially small particle) lipoproteins (plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL), (see apoA-1 Milano). It is commonly referred to as a hardening or furring of the arteries. It is caused by the formation of multiple plaques within the arteriesThe atheromatous plaque is divided into three distinct components:

#The atheroma ("lump of wax", from Athera, wax in Greek,), which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery.
#Underlying areas of cholesterol crystals .
#Calcification at the outer base of older/more advanced lesions.

CAUSES:

Atherosclerosis develops from low-density lipoprotein molecules (LDL) becoming oxidized (ldl-ox) by free radicals, particularly oxygen free radicals (ROS). Blood in arteries contains plenty of oxygen and is where atherosclerosis develops. Blood in veins contains little oxygen where atherosclerosis rarely develops.

When oxidized LDL comes in contact with an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. The LDL molecule is globular shaped with a hollow core to carry cholesterol throughout the body to generate brain tissues, vitamin D, and so on. Cholesterol does not dissolve in water. Blood is 70% water. Cholesterol can move in the bloodstream only by being transported by LDL.

The body's immune system responds to the damage to the artery wall caused by oxidized LDL by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. Unfortunately, these white blood cells are not able to process the oxidized-LDL, and ultimately grow then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle.

Eventually, the artery becomes inflamed. The cholesterol plaque causes the muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure.

Some researchers believe that atherosclerosis may be caused by an infection of the vascular smooth muscle cells. Chickens, for example, develop atherosclerosis when infected with the Marek's disease herpesvirus. Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation.Cholesteryl ester accumulation is associated with atherosclerosis.

SYMPTOMS:

Atherosclerosis symptoms are not due to pain produced by a partially obstructed artery, but to an inadequate amount of blood received by the arteries’ tissues. The severity of symptoms depends on the extent of the blockage or narrowing, on whether there are alternate arterial branches, and on the tissues’ demand for oxygen.

Symptoms of blocked arteries occur under stress, when a greater blood supply is needed than when a person is relaxed. Symptoms are particularly evident in blocked arteries of the lower extremities in which feelings of heaviness, pain and cramping appear during walking. This is why atherosclerotic patients are likely to stop frequently when they walk.

Because of the way nerves are connected to the heart, it is not always easy to pinpoint the exact cause of the pain.A patient may often describe a cardiac condition as indigestion or "a feeling of pressure"in the stomach or inside the chest, which radiates in the neck, the jaw or the left arm.
At times pain is severe, but at other times it may simply seem like a muscle contraction. This wide variation can affect a doctor’s diagnosis, may cause its delay or, even worse, lead to a misdiagnosed condition. Usually, the first symptom is an attack characterized by pain in the chest (angina pectoris).

With narrowing of the intestinal arteries, pain may be acute (stabbing pain) and sudden. In cerebral atherosclerosis (narrowing of the brain’s arteries) there are usually no signs of blockage until an artery is completely obstructed.

Atherosclerosis Treatment:

An Introduction:

There's no getting around it: Atherosclerosis changes your life. For many people, living with a condition caused by atherosclerosis requires changes both big and small, from undergoing major surgery to adding more fruits and vegetables to their diets. Change can be difficult, and sometimes even scary. But with support, resources, and a good supply of determination, most people are able to meet these new challenges well.

Atherosclerosis treatment will vary for each particular situation. Everyone diagnosed with atherosclerosis will need to undergo lifestyle changes. Depending on the severity, these may be the only changes a person needs to make. For more serious conditions, atherosclerosis treatment may include medications or certain procedures.

Lifestyle Changes as Part of Atherosclerosis Treatment:

If you have atherosclerosis, you know by now that it's vital to control it. Making lifestyle changes that improve your atherosclerosis risk factors is one important part of atherosclerosis treatment. Eating well, getting regular physical activity, and maintaining a healthy weight will help to lessen the severity of your condition. If you smoke, you'll need to quit. Reducing stress and limiting alcohol use can also improve your heart health. And if you have diabetes, you will need to carefully manage it. Be sure to see your doctor regularly for followup visits.

There are a number of links related to lifestyle changes available on eMedTV. Some include:

DASH Diet for high blood pressure
Low Cholesterol Diet for high cholesterol
Diet and Heart Disease for heart disease
BMI Calculator or BMI Chart to find your ideal weight.

There are also articles about lifestyle changes with regards to heart disease that also apply to other conditions caused by atherosclerosis. Some include:

Smoking and Heart Disease
Heart Disease and Exercise
Stress and Heart Disease
Alcohol and Heart Disease
Weight and Heart Disease
Obesity and Heart Disease.

PREVENTION:

Atherosclerosis (AS) can not only be prevented, but is also reversible if certain measures are taken into consideration and acted upon:

A high-fat diet is the main risk factor. Diets high in fat increase circulating cholesterol and triglycerides, which cause the formation of atherosclerotic plaque inside the arteries.

Uncontrolled hypertension is well-known to increase cardio-circulatory damage. Blood pressure levels higher than 140/90 contribute to AS. Currently these levels are considered borderline at best, and efforts should be made to attain lower levels.

Smoking: in the United States, cigarette smoke causes 180,000 deaths a year due to vascular conditions. Statistically a smoker lives seven years less than a non-smoker.

Diabetes control: this disease causes circulatory problems, increasing the risk of AS.

Weight control: being overweight places an excessive burden on the heart and limits exercise activity

Practicing regular physical exercise: exercise reduces cholesterol and blood pressure levels and keeps the cardio-circulatory system in good condition

Reducing stress and depression: these mental states often lead to higher blood pressure levels which tend to become chronic, and indirectly, to increased appetite, hypertension and lack of exercise.

Genetic history: learning whether your family has a history of circulatory diseases may help prevent the onset of AS.

How High Cholesterol Leads to Atherosclerosis:

High cholesterol levels lead to clogged arteries in a process called atherosclerosis. Lowering cholesterol lowers the risk of diseases caused by atherosclerosis, like heart attacks and strokes.

What makes cholesterol so bad for your arteries? And isn't there a "good" cholesterol? How does treating high cholesterol help?
Cholesterol and Atherosclerosis: The Bad, the Good, and the Ugly

In cholesterol and atherosclerosis, there are good guys and bad guys:

"Bad" cholesterol, also called low-density lipoprotein (LDL), has chemical properties that can damage arteries. Damaged areas allow more LDL to penetrate artery walls. The LDL gets stuck and accumulates in the artery's wall.

Inside the artery wall, free radicals transform LDL from something bad to something worse: oxidized LDL. The cholesterol chemical spill attracts white blood cells and other cells to try to clean up the mess. The cells chew up and digest oxidized LDL.

Once begun, this whole process tends to continue. Over years, the deposit of "bad" cholesterol, cells, and debris grows larger, and it's called a plaque.

"Good" cholesterol, known as high-density lipoprotein (HDL), is the yin to LDL's yang. HDL is on your side: it circulates through your body, acting like a cholesterol magnet. HDL diverts and delivers cholesterol away from your arteries. Much of the cholesterol is either eliminated from the body, delivered to tissues such as the liver, or used to make hormones.

As cholesterol plaques form and grow inside arteries, they eventually can begin to block off blood flow. Here's where atherosclerosis gets ugly.

The LDL-rich center of the plaque can be stable, meaning it grows in a slow, controlled way. The plaque may eventually cause symptoms, but generally speaking, the body adapts. These blockages seldom cause heart attacks.

Plaques can instead be unstable. Remember the cells inside the plaque, digesting all the LDL? As they work, these cells release enzymes that dissolve some of the biological "duct tape" (collagen) holding the plaque together.

Unstable plaques are prone to tearing. If they rupture, they release material that causes a blood clot to form inside the artery. Within minutes, blood flow is cut off. The result: a heart attack or stroke.

Cholesterol Treatment:

Down With the Bad, Up With the Good

The link between cholesterol and atherosclerosis led to treatments to improve cholesterol levels. Numerous medications, and changes in lifestyle, can improve cholesterol and reduce atherosclerosis.

Exercise with or without weight loss increases "good" HDL cholesterol and reduces the risk of heart attacks and strokes.

A diet high in fiber and reduced fats can lower "bad" LDL cholesterol. Plant-derived stanols used as fat substitutes also help lower cholesterol.

Statins are the most-often prescribed medicines for high cholesterol. Statins can dramatically lower "bad" LDL cholesterol, by up to 60% or more. They can also increase HDL modestly. In studies, statins reduce the rates of heart attacks, strokes, and death from atherosclerosis.