Figure 1: Structure of medium sized muscular artery [10].








1.2 Tissue Structure and Properties

There are four different types of arteries: elastic, medium muscular, small arteries and arterioles.  The structure of the arterial wall is anisotropic and non-linearly elastic, which makes the properties extremely non linear[8].  Typically, the ways in which different compositions of collagen, elastin and protein are linked dictate the overall mechanical properties of the arterial wall.  It has been shown that when the elastin ratio is higher than the collagen ratio, the elastic modulus decrease and extension is increased [8]. Artery walls consist of smooth muscle fiber which contracts and relaxes under the instruction of the sympathetic nervous system for the transport of oxygenated blood away from the heart with the exception of the pulmonary artery.  Arteries are elastic vessels that transport blood away from the heart.  The artery wall consists of three layers: the tunica adventitia, tunica media, and the tunica intima. 

1.2.1 Tunica Adventitia

The tunica adventitia is the strong outer layer of arteries and veins. Within the tunica adventitia of arteries are small blood vessels which send penetrating branches into the media to supply it with blood.   The adventitia contains the tissue thromboplastin which promotes blood clotting, but lacks elastic lamellae, which are important for regulating contractile and elastic tension in mechanically stressed vessels. The fibers allow the arteries and veins to stretch to prevent overexpansion due to the pressure that is exerted on the walls by blood flow.  Connective tissues function primarily to support the body and to bind or connect all types of tissues, and is characterized by the large amounts of intercellular matrix that it contains.  There are relatively few cells which are responsible for secreting the matrix.  Within the matrix are a variety of connecting and supporting fibers.  Connective tissue typically has cells scattered throughout an extracellular matrix.  There are several types of connective tissue, with the most common being loose connective tissue which holds organs in place and attaches epithelial tissues to other tissues.  Loose connective tissue has a ‘weave’ like structure and three main types of fibers: collagenous fibers, which are made of collagen and consist of bundles of fibrils that are coils of collagen molecules; elastic fibers, which are made of elastin and are stretchable and reticular fibers which join connective tissues to other tissues; and fibrous connective tissue, which is found in ligaments and tendons and is composed of large amounts of closely packed collagenous fibers. Lastly, there are specialized connective tissues, which include adipose, cartilage, bone, and even blood.  Blood is considered a type of connective tissue even though it has a significantly different function in comparison to other connective tissues. However, it does have an extracellular matrix, the plasma, which contains erythrocytes, leukocytes and platelets. This layer is formed from irregularly arranged collagen bundles, scatter fibroblasts, some elastic fibers, and even blood vessels within a blood vessel, known as vasa vasorum [9]. Fibers

Connective tissues consist of cells separated by varying amounts of extracellular matrices.  Cells typically only account for a small fraction of the tissue volume of connective tissues [10]. The extracellular matrix consists of fibers imbedded in the substance containing tissue fluid.  There are three types of fibers in connective tissues: collagen fibers, elastic fibers, and reticular fibers. Collagen fibers are the main type in most connective tissues, with the primary function of adding strength to the connective tissue.  Fibers can vary in size from one to ten microns; visible longitudinal striations indicate that fibers are composed of thinner collagen fibrils, which in turn are composed of microfibrils. The microfibrils are a compilation of three collagen molecules in a spiraled triple helix called tropocollagen. Different types of tropocollagen give fibers structural and functional characteristics which are specific to where the fiber is found.  Typically collagen fibers stretch about fifteen to twenty percent.

There is no evidence of any substructure in the elastic fibers [10].   Elastic fibers consist of individual microfibrils which are embedded in an amorphous matrix.  The matrix accounts for about ninety percent of the fiber and is composed of elastin protein.   Elastin fibers can be stretched to about one hundred and fifty percent of their original length.

Reticular fibers form a fine network rather than bundles [10]. It has been noticed that reticular fibers form cross striations with the same periodicity as that in coarse collagen fibers.   Although reticular fibers consist of collagen, they main type of tropocollagen found in reticular fibers is different from that found in the coarse collagen fibers.  Reticular fibers provide support to individual cells. Connective Tissue Cells

Connective tissue cells are typically divided into two types, fixed cells and wandering cells [12]. Fibrocytes, or fibroblasts and fat cells are fixed cells, where as macrophages, monocytes, lymphocytes, plasma cells, eosinophils and mast cells are wandering cells.

Fibrocytes are the most common cell type in connective tissues.  If fibrocytes are stimulated by damage to the surrounding tissue, the fibrocyte is altered into a fibroblast [10]. The fibroblasts contain organelles that are necessary for thde synthesis and excretion of proteins needed to repair the tissue damage.  Fibrocytes usually do not leave the connective tissue.  Reticular cells are usually larger than fibrocytes.  Reticular cells are the fibrocytes of reticular connective tissue and form a network of reticular fibers.  Adipocytes are fat cells that are fixed cells in loose connective tissue.  Their main function is the storage of lipid.  Macrophages arise from monocytes.  Monocytes originate in the bone marrow upon which they are released into the blood stream.  They are mobile and leave the blood stream to enter connective tissues where they differentiate into marcophages.

The fibroblasts are the most important in the connective tissue.  Fibroblasts manufacture and maintain the extracellular material.  They migrate throughout the extracellular matrix to wherever they are needed.  Adipocytes are cells that are very efficient at storing energy in the form of triglycerides. 

1.2.2 Tunica Media

The Tunica media is the middle layer of the walls of arteries and veins and is the thickest.  It is composed of smooth muscle cells, connective tissue, elastic tissue and in larger arteries, elastic fibers.    It is this layer that gives the arterial wall its mechanical properties.  It is comprised primarily of circumferentially arranged smooth muscle cells.  The smooth muscle is reinforced by organized layers of elastic tissue which form elastic laminae.  The internal elastic lamina separates the tunica intima from the tunica media.  The external elastic lamina usually separates the tunica media form the tunica adventitia.  The tunica media also contains autonomic nerves.  Elastic tissue is very well developed, since it receives the full thrust of the systolic pressure wave close to the heart.  Between the smooth muscle layer and the adventitia are another layer of elastic fibers known as the elastic externa.  All in all, the tunica media consists of a layer of elastic fibers, or the elastica interna layer, a layer of smooth muscle cells and elastic fibers with elastic lamellae and smooth muscle cells imbedded in a matrix, and another layer of elastic fibers, or the elastica externa.

The characteristic notable to the tunica media is the unstriated muscle fibers. The tunica media’s layer of smooth muscle cells can contract and relax to control the blood pressure and flow in the artery.  Elastic tissue and collagen in the media along with the elastic tissue in the internal elastic lamina increase the elasticity and strength of the wall of the artery, as the artery contracts and relaxes. Smooth Muscle

Text Box: Figure 3: Cross sectional microscopic view of an artery.  Red depicts smooth muscle, black depicts connective tissue (elastic), and blue depicts collagen [12].
The smooth muscle comprising the tunica media is responsible for the contractility of the blood vessel.  Most notable about the smooth muscle is the considerable deficiency of visible cross striations.   Smooth muscle can be classified into single and multi unit smooth muscle.  The fibers are assembled in different ways.  In the single unit muscle fibers are gathered into dense sheets or bands, and although they are somewhat parallel, they are densely and irregularly packed together, usually so that the narrower portion of one fiber lies against the wider portion of the next.   The fibers have connections, the plasma membranes of two neighboring fibers form gap junctions that act as low resistance pathways for the rapid spread of electrical signal through the tissue.  The multi unit smooth muscle fibers do not have interconnecting bridges.  Rather, they are mingled with connective tissue fibers.  Smooth muscle is predominantly under the control of autonomic nervous system.  The single unit smooth muscle has regions where contractions are spontaneously and rhythmically produced.  The layer of smooth muscle cells in the media are concentric waves of cells intermixed with elastic fibers.  Elastic lamellae and smooth muscle cells are imbedded in a matrix that is rich in proteoglycans, which are formed of disaccharides bound to protein.  The proteoglycans serve as a binding material in the interstitial spaces [11].

1.2.3 Tunica Intima

The tunica intima the inner most layer of the artery.  The intima consists of three layers; a layer of endothelial cells lining the lumen, or the central blood carrying canal of the vessel, a sub-endothelial layer made up of mostly loose connective tissue, and the outer most layer consisting of a thin membrane of connective tissue.  The lining layer consists of highly specialized multifunctional flattened endothelial cells, or endothelium, that is covered by elastic tissues.  This sits on a basal lamina which beneath is a very thin layer of fibrocollagenous support tissue.  The thin layer of connective tissues serve to anchor the cells to the arterial wall. This layer in the only layer that is present in all blood vessels. 

The inner most layer of the intima is lined with nucleated endothelium, which consist of flat, irregular, oblong cells [13].    Next, is a thin, finely granular layer of fibers and spindle shaped or stellate protoplasmic cells embedded in a system of plasma canals.  Lastly, the inner elastic layer which is just a fibrous elastic membrane united by connective tissue.  Larger arteries have longitudinal fibers situated between two elastic plates.  This is responsible for maintain the appropriate lumen width. Endothelial Cells

The tunica intima is lined by endothelial cells, or the endothelium.   Endothelial cells have many functions.  Endothelial cells are very flat and form brick like patterns on the inside of arteries and vessels.  The cells overlap at junctions between cells to help seal the vessel [10].  The intercellular junctions are vital for the integrity of the vessel by limiting the flow of material in and out of the wall.  Depending on the function of the particular wall, the endothelium layer will be tightly sealed as resulting in highly selective transport across the membranes, or have holes to allow for rapid passage of larger molecules or fluids.

Endothelial cells are selective filters which regulate the passage of gases, fluids, and other molecules across the cell membranes.   The endothelial cells act as receptors and interaction sites for many important host molecules, especially those that attract or repel leucocytes.  Leucocyte adhesion molecules are important in the wound healing process, namely inflammation.  Normally they are repelled by endothelium to allow blood cells to flow, but during an inflammatory response these cells are attracted to the endothelium.  Diapedesis, a process in which the leucocytes pass through the endothelium layer, is also a normal function.  The process of diapedesis occurs often and by many different types of cells to gain access to tissues.   The endothelial cells also produce Factor VIII which is vital to blood clotting, another step in the wound healing process.  Additionally, endothelial cells are responsive to many local agents including histamine.  As a result, endothelial cells open up their intercellular junctions to allow fluid passage from blood plasma to the surrounding tissues.  These and other related procedures are a part of the inflammatory response.