Atherosclerosis Heart Disease
Atherosclerosis heart disease, also known as artery disease,
is the 20th century epidemic. It accounts for almost 500,000
deaths every year in the United States alone. The basic cause
of coronary artery disease is a buildup of abnormal lipid
and fibrous plaques (atheromas) that narrow the coronary arteries
and deprive the heart of the blood and the oxygen it needs.
The major risk factors may be controlled through proper diet,
physical activity, and smoking cessation. In conjunction with
risk management, there are a number of therapeutic and life-saving
pharmaceuticals available and better drugs with fewer undesirable
side affects are constantly in the pipeline. Traditionally,
the preclinical process of drug development includes animal
model studies and miniature swine are probably the best models
for human cardiovascular disease.
Pigs as Models for Research
Pigs have been used for 40 years as models for research into
cholesterol and lipoprotein metabolism with application to
atherogenesis. The pig is an excellent model for human cardiovascular
research because of a number of similarities to the human.
The anatomy of the coronary arteries and the pattern for development
of collateral circulation after permanent ischemic episodes
are two important similarities. Development of atherogenic
lesions in arteries of humans is a gradual process that begins
very early in people consuming the typical U. S. diet that
is high in fat and cholesterol.
Pigs naturally develop atherosclerosis; aortic streaks are
observed in young pigs within a few weeks when diets are high
in fat (particularly saturated fat) and cholesterol. The full
blown lesion that produces partial occlusion of arteries does
not appear until experimental diets are fed for months but
the pathological state may be hastened by denuding the arterial
intima.
There is evidence for inheritance of the propensity toward
atherogenesis in pigs as in humans. Genetic mutations of miniature
swine that are predisposed to hypercholesteremia have been
identified, developed and maintained [Arterioscler Thromb,
12:647-656]. Pigs also have been used successfully to investigate
the regression of atherosclerotic plaques. In humans and in
pigs, the predominant bloodborne cholesterol transporter is
low density lipoprotein (LDL). Comparison of the serum lipoprotein
pattern among several mammalian species indicates the pig
is probably the most similar to the human.
There have been many diverse studies of nutritional influences
on cholesterol and lipoprotein metabolism in miniature swine.
Scientists have examined the various dietary fat sources with
a wide array of fatty acid compositions, including the currently
popular fish oils, protein sources, particularly comparisons
of plant and animal proteins, minerals, fiber sources and
other dietary factors including pharmacologically active materials.
Minipigs are favorable models for nutritional studies related
to cholesterol and lipoprotein metabolism because they are
omnivorous, as are humans.
Miniature Swine vs. Commercial Swine
Miniature swine are preferable to commercial swine as animal
models because they maintain weight and size throughout adulthood
that is similar to an adult human male. They are docile and
easily handled, and they have striking physiological similarities
to human digestive and cardiovascular systems.
Sinclair is experienced in producing atherosclerotic miniature
swine for in-house studies or for scientists located at other
institutions. Furthermore, Sinclair has access to fluoroscopy,
IVAS, treadmills, and related equipment and expertise related
to cardiovascular studies. Please contact us to discuss your
needs. |