Atherosclerosis, or "Hardening of the Arteries"

- Is the leading cause of death in America

- Reduces blood flow and oxygen delivery to the heart, brain, legs, kidneys and other organs, resulting in disease and degeneration.

- "Athero" is from the Greek word "gruel" (the cholesterol/fat deposits)

- "Sclerosis" is from Greek for "hardness" (collagen as scar tissue and calcification as calcium deposits are usually 70% of plaque)

Major Risk Factors for Atherosclerosis
(out of 246 recognized risk factors)

- Hypertension (high blood pressure)
- Smoking
- Diabetes
- Elevated Serum total cholesterol
- Decreased High Density Lipoprotein levels
- Obesity
- Stress
- Sedentary Lifestyle
- Chronic Infections
- Heavy metal accumulation
- Dietary deficiencies
- Anything and everything that injures the blood vessel wall

Blood Vessels and Oxygen Delivery to the Tissues

Red Blood cells (erythrocytes) transport oxygen to the cells and carry carbon dioxide (cellular waste) back to the lungs to be exhaled.

Veins are thin walled blood vessels that carry blood lacking oxygen
back to the heart.

Capillaries are microscopic blood vessels having only one layer of endothelial cells as a wall. This thin wall allows oxygen and nutrients
to move into the cells easily and carbon dioxide to move easily into
the capillaries and be carried back to the lungs.

The Artery

An Artery has Three Layers:

(1) The inner lining (the endothelium) promotes the smooth and unrestricted flow of blood across its surface.

(2) The middle or muscular layer is used to regulate the blood flow to various organs as the oxygen demand changes. For example, more blood flows to your arm when it is waving or to your stomach when it is digesting.

(3) The outer layer (Adventitia - collagen) helps maintain the structure of the two inner layers as they respond to the changes in blood pressure.

The Artery Wall should expand and contract with the heartbeat. If the artery does not expand, the heart has to work harder to push the blood into the artery and the blood pressure rises.

The Endothelial Cells (The inner lining)

- Form a barrier to prevent harmful substances from entering the arterial wall.

- Sense the blood pressure and flow rate and release nitric oxide which relaxes the vessel walls to allow more blood to flow through.

- Sense damage and produce reparative growth factors.

- Normally have an outer coating of a negative electrical charge which turns positive if the cell's surface is injured. This positive charge attracts the negatively charged white blood cells, red blood cells and platelets and initiates the process of blood clotting.

- Signal blood cells to stick to the endothelial cells (platelet aggregation/clotting) to prevent the loss of blood.

Major Causes of Endothelial Injury

- Shear stress - friction of blood against the lining

- Hypertension (also related to shear stress)

- Sympathetic neurotransmitters - noreipinephrine, epinephrine, and dopamine (flight or fight stress response)

- Stress induced hormones such as cortisol, IL-6, ADH.

- Diabetes (glycosylated proteins, insulin resistance)

- Chemical toxins (pesticides, herbicides, etc)

- Air and water pollution/Heavy metal poisoning (mercury, lead, cadmium, arsenic, etc.)

- Tobacco smoke

- Cholesterol, especially oxidized LDL and VLDL

- Excess Salt in Diet

- Free Radicals (molecules with unpaired electrons)

- Infectious agents
- Chlamydia pneumoniae
- Helicobacter pylori (as with peptic ulcer lesions)
- Herpesvirus
- Cytomegalovirus
- Candida Albicans (inhibits endothelial relaxation)
- Inflammation/Allergies/autoimmunity

- Homocysteine

- Low dietary calcium (stimulates Hyperparathyroidism and transporting calcium from the bones to the soft tissue)

- Excess alcohol consumption is associated with an increase in free radical damage and increased risk of coronary heart disease (CHD) and stroke.

How Atherosclerotic Plaque is formed

Healthy blood vessel - Endothelial injury - Development of foam cells and plaque

Injury to the endothelial cells stimulates white blood cells (monocytes) to stick to the blood vessel wall.

These monocytes damage the endothelial barrier by oxidizing the endothelial surface. This changes the permeability of the endothelium and allows cholesterol, triglycerides, fibrinogen, etc. to enter into the wall of the artery.

Inside the artery wall, free radicals oxidize LDL and VLDL cholesterol, creating a chain reaction of cellular damage.

As the monocytes (which change into macrophages) invade the inner layer of the artery, they digest the rancid lipids to become "foam cells" (macrophages filled with fat globules).

Foam Cells

The development of fatty streaks and intimal thickening -

The development of blood clots -

Increasing plaque and thrombus -

- Form fatty streaks
- Earliest visible lesion in atheroslcerosis
- Mostly lipid engulfed macrophages with occasional lipid filled smooth muscle cells
- Seen as early as age 3.

The collagen calcifies and becomes hard and brittle, like bone, reducing the elasticity of the blood vessel wall. This combination of foam cells, calcification, and lipids is called "atherosclerotic plaque". If the plaque's surface breaks, platelets stick to this damaged surface and blood clots form on the surface of the plaque. If the surface break is small, only a microscopic blood clot will form. This tiny blood clot is immediately broken into small pieces (called fibrino peptides) by a clot dissolving enzyme system - the fibrinolytic system.

If the plaque surface break is more extensive, more clots form and the fibrinolytic system cannot dissolve the clot faster than it can form. This gradually causes a large clot to form. The artery becomes clogged and a heart attack or stroke occurs.