| 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 undesireable 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 lowdensity 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.
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