Monday, January 19, 2009


Atherosclerosis is a disease more commonly referred to as a 'Hardening of the arteries' (1), and is the major cause of morbidity and mortality in the western world (2). It is believed to be a multifactorial process, which can in some cases start in utero (3). Patients with atherosclerosis represent a heterogenous group of individuals, with diseases that progress at significantly different rates and in distinctly different patterns (5). It is described by the deposition of fatty material (atherosclerotic plaques) in, not on, arterial vessel walls - due to an excess in-flow of cholesterol. This can lead to occlusion of the artery - in most cases this occurs due to a sudden rupturing of the plaque that triggers the emergence of a blood clot/thrombus that blocks blood flow (as oppose to direct occlusion by the plaque) leading to complications such as strokes or heart attacks (1/4).

There are many risk factors for this disease: diet and lifestyle (environment) works synergistically with genetic factors predisposing to or protecting from the disease. Understanding the complexity and functional relevance of these risk factors especially the genetic factors can improve the early detection, management and prevention of this disease.
This essay will review some of these genetic factors (both predisposing and protecting) and discuss their contribution to the risk of developing Atherosclerosis.

Predisposing factors:
There have been many predisposing factors discovered using clues from the pathology of the disease including genes/proteins associated with blood lipids, endothelial cell changes (lipid deposition), macrophage responses, inflammation, oxidative damage, vascular repair control, thrombosis and diabetes/obesity (1).

Blood lipids: One of the most important risk factors for atherosclerosis is dyslipidemia (quantitative and qualitative changes in plasma levels of lipids and lipoproteins), (3). Atherogenic dyslipidemia has been genetically linked, is characterized by increased plasma triacylglyceride and apolipoprotein (apo) B levels, low HDL concentrations and the development of small dense LDL particles (8), and predisposes for atherosclerosis. HDL in particular is very important in the reverse cholesterol transport (RCT) pathway which is the major protective system against atherosclerosis (7), (clears excess cholesterol from arterial cell walls (6)). It has been found that a cellular ATP-binding cassette transporter (ABC) called ABCA1 mediates the first step of RCT. Mutations in ABCA1 cause Tangier disease (TD), a severe HDL deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. Studies of TD heterozygotes revealed that ABCA1 activity is a major determinant of plasma HDL levels and therefore predisposes for coronary vascular diseases such as atherosclerosis (6). Evidence from epidemiological studies suggests that the development of small, dense LDL (LDL subclass phenotype B) can also be genetically influenced (15/16). Other factors genetically linked to the changes in blood lipids include: liver x receptors (LXR's). LXR's (LXRalpha and LXRbeta) are nuclear receptor transcription factors that are activated by certain oxysterol derivatives of cholesterol. Millatt et al reported that LXR's play an important role in the response to excess cholesterol and by using an LXR agonist (Ghr3965) they were able to demonstrate a dramatic anti-atherosclerotic effect in mice (11). This can be taken as evidence of a genetic link of LXR genes to atherosclerosis.

Endothelial cell changes: endothelial dysfunction is characterised by reduced bioactivity of nitric oxide (NO). Channon et al reported an important role for both the NAD(P)H oxidases and endothelial NOS in the increased vascular superoxide production associated with endothelial dysfunction predisposing human vascular disease states (10).
Macrophage responses: During the process of atherosclerosis, the homeostatic mechanisms (which are genetically controlled) of a macrophage fail and uncontrolled cholesterol deposition is promoted by the scavenger functions of the macrophages (12).
Diabetes/Obesity: People with diabetes tend to be predisposed to atherosclerosis due to their accelerated synthesis of LDL's (3).

Protective factors:
There have been a lot less factors (genetically linked) identified that protect against the development of atherosclerosis. It is known however that pre-menopausal women are to a degree protected from developing the disease. Walters et al reports that oestrogen deficiency in postmenopausal women may contribute to endothelial dysfunction, together with other modifiable risk factors and that the absolute risk of coronary disease is greater for men than for pre-menopausal women (13). This suggests that oestrogen somehow protects women from atherosclerosis.

Most risk factors for atherosclerosis are associated with impaired endothelium-dependent vasodilatation due to reduced NO production. Folate/folic acid not only reduces plasma homocysteine levels but also enhances eNO synthesis and shows anti-inflammatory actions thereby also providing protection against the development of atherosclerosis (14). The LPL S447X cSNP has been reported to be associated with decreased blood pressure and plasma triacylglycerides and increased high-density lipoprotein cholesterol (all atherosclerosis risk factors) (17). Clee et al reported a reduced risk of coronary artery disease suggesting that this polymorphism is protective against atherosclerosis. Observations that apoE deficient mice develop spontaneous atherosclerosis, whereas transgenic mice expressing a defective apoE from the liver do not, suggesting that macrophage apoE secretion may indeed play a protective role in regard to atherosclerosis susceptibility (2).

Atherosclerosis is a multi factorial process that can start in utero, it progresses over decades and leads to cardiovascular complications such as heart attacks and strokes. This disease accounts for a large proportion of morbidity and mortality in the western world and is affected by both environmental and genetic risk factors. Understanding the complexity and functional relevance of these risk factors especially the genetic factors (predisposing to or protecting from) can improve the early detection, management and prevention of this disease.
For example, mutations in the ABCA1 gene lower HDL levels thereby predisposing the subject to atherosclerosis. Knowing how this mutation affects the development of atherosclerosis allows for possible gene/protein therapy methods to be investigated. It is also known that macrophage apoE secretion may play a protective role in regard to atherosclerosis susceptibility, therefore methods can now be investigated as to possibly inducing apo E synthesis/secretion to help protect patients with a high risk of developing the disease.

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Achilles Tendonitis

Dancers, as well as many other athletes, are extremely prone to many injuries, in particular, injuries to the foot and ankle. One of the most common among these injuries that are seen notably in dancers is called Achilles Tendonitis.

Achilles Tendonitis is derived from the Greek legend of Achilles. The term Achilles Tendon is derived from this myth in which the Greek god Achilles was dipped in the river Styx to become immortal. The back of his ankle did not touch the water, therefore rendering his ankle vulnerable to common human pain. This is why the tendon that runs down the back of the ankle is known as the Achilles Tendon, and as the story goes, can cause much pain when injured. (Coussins, p.1)
Unlike most tendons in the human body, the Achilles Tendon lacks its own rich blood supply. Because of this lack of a rich blood supply, many dancers are consequently prone to injury and chronic Achilles Tendonitis. The severity of Achilles Tendonitis may vary from a mild irritation and inflammation, to the thinning of the fibers themselves. This can lead to swelling, and more severely leading to adhesions between the tendon and its sheath. (Dance Technique, p.1)
Symptoms of Achilles Tendonitis can be very deceiving. Sharp pains a dancer may experience can subside while dancing and then return before completing the dance or production. This is a problem because one can further injure themselves when this scenario occurs. Achilles tendonitis in dancers can be caused by many factors. These factors may include ignoring heel pains, overworking the feet and ankles, overstretching (as well as not stretching enough), breaking in new shoes (also not wearing supportive shoes), and most commonly, not warming up and cooling down properly. (Coussins, p.2) With all of these factors, a dancer can easily develop any form of Achilles Tendonitis, or other injuries. Another reason many dancers are susceptible to Achilles Tendonitis can be associated with the fact that they work in a plantar flexion, which is the extension of the ankle resulting in the forefoot moving away from the body. Consequently, dancers develop tighter heel cords than the average person. Also, in dancers it is almost impossible to avoid stretching the Achilles while dancing. Many positions dancers use frequently may place an extra strain on the Achilles, particularly a position of low releve. With a bone prominence in the posterior superior portion (upper back portion) of the calcaneus (heel bone), the condition is more likely to occur because the bone and tendon rub together. This can be a problem for many dancers who may take short leaves of absence, and then upon returning to dance they may instantly see symptoms again.

Treatment for Achilles Tendonitis varies from person to person. Complete inactivity would probably be considered the best treatment along with anti-inflammatory medication, and applications of ice and heat. There are other medical treatments available for this pain. To lessen the amount of fluid build up, as well as to control pain, there are a plethora of anti-inflammatory medications available. Ultrasound therapy is also a fairly new form of treatment. The high-frequency waves are transmitted through a tens unit and will stimulates damaged tissue, healing the tendon faster. (Dance technique, p.2) It would be most imperative for the dancer to wear heel lifts in their shoes on a daily basis, when walking, running, or dancing.

Although many dancers may put themselves in high-risk situations regarding their health, they continue to do it with passion. Prevention of injuries with particular attention to the Achilles Tendon is one of the most important aspects self care in the dancing world. A dancer providing care and concern for his or her body will be able to maintain their dancing activity as long as possible, and with much less pain to endure. Taking care of something as simple as one’s Achilles tendon will provide one with a greater benefit in their present and future dancing careers.

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