Biomedical Engineering Reference
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disease. Several models of cardiac hypertrophy are available in small laboratory
animals such as the rat, and proteomic studies have been done in large animal
models such as bovine DCM.
The comparison of 2DGE patterns from DCM patients with those of controls has
revealed statistically significant intensity differences which forms the basis of a
human myocardial 2DE database. The number of proteins that can be identified is
limited only by the capacity of a laboratory and the personnel rather than by the
principle of feasibility. Specific proteins are hyperubiquitinated in diseased hearts.
These proteins can be purified by affinity chromatography and identified using 2D
PAGE/MALDI-TOF. The ubiquitin-proteosome pathway is a possible target for
therapeutic intervention in heart disease.
Role of Proteomics in Heart Transplantation
Heart transplantation is now an established procedure for treating patients with end-
stage heart failure. During the past 20 years, the number of heart transplants per-
formed worldwide has increased from a few to approximately 4,000 per year. Major
problems following heart transplantation include infection with cytomegalovirus
(CMV) and rejection − hyperacute, acute, or chronic. Hyperacute rejection is the
failure or rejection of graft with the first 24 h. Acute rejection is the major risk for
survival in the first posttransplant year. It is usually monitored by regular endomyo-
cardial biopsy and histological examination. One-year survival in heart transplanta-
tion is 85%, and 50% of the grafts are lost after 5 years.
Proteomics is being used to develop noninvasive methods for detecting acute
rejection after cardiac transplantation. Mass spectrometry analysis identifies a set
of proteins in the heart altered with acute or chronic rejection. ELISA (enzyme-
linked immunosorbent assays) have identified proteins in serum samples of patients
that are potential noninvasive biomarkers of acute and/or chronic rejection.
Validation of these diagnostic markers requires analysis of larger sets of patient and
serum samples. Early detection of rejection is important as it provides an opportu-
nity for treatment with immunosuppressant therapy.
Future of Application of Proteomics in Cardiology
Proteomic analysis has provided important insights into ischemic heart disease,
heart failure, and cardiovascular pathophysiology. The future holds great promise
for the availability of a panel of cardiac serum biomarkers able to delineate differ-
ent stages of each heart disease, thus allowing the design of clinical interventions
potentially using stage-specific therapeutics. All of this is feasible only with
detailed information about the unique and selective protein modifications that occur
during the development of heart disease. The combination of proteomic biomarkers
with clinical phenotypes and genetic haplotype information can lead to a more
precise diagnosis and therapy of heart disease on an individual basis − personalized
cardiology (Arab et al.
2006
).
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