Cardiovascular Therapeutics - Applications of Biotechnology in Cardiovascular Therapeutics - page 8

1 in 500 persons is a heterozygote. Homozygotes are extremely rare with an incidence
of 1 in one million. Patients with hypercholesterolemia manifest skin deposits of
cholesterol called xanthomas and atherosclerosis. Most of the untreated patients die
of coronary artery disease at a young age. Current therapy is a combination of diet
to decrease cholesterol intake and statins. However, a number of patients are still
failing to reach treatment guidelines even with the most effective of the currently
available statins.
The Endothelium as a Target for Cardiovascular
Therapeutics
The endothelium is a complex organ system that controls the homeostasis of the
vasculature by integrating signals between the vascular wall and the vessel lumen.
Under physiological conditions, it maintains a normal vascular tone and blood
fluidity by elaborating a variety of factors, such as nitric oxide, prostacyclin, and
endothelin. Disturbances of the endothelium can produce vasoconstriction,
inflammation, and thrombotic events and manifest in various disorders such
as hypercholesterolemia and hypertension. There are several causes of altered
endothelial functions and the mechanisms underlying them are complex and
not yet fully understood. There is substantial evidence that many endothelial
functions are sensitive to the presence of reactive oxygen species and subse-
quent oxidative stress. Exogenous antioxidants can modulate the endothelium-
dependent vasodilation responses, the endothelium-leukocyte interactions, the
balance between pro- and antithrombotic properties, and the vascular apoptotic
responses.
Molecular Cardiology
Advances in genomics and achievements of the Human Genome Project had an
enormous impact on medicine, giving rise to the term genomic medicine. This has
also changed the classic practice of clinical cardiology in many ways, increasing
our awareness of inheritance of defective genes and their impact on health and
disease, and providing new diagnostic and therapeutic tools as discussed under
cadiogenomics. Proteomics has a further impact on cardiology and will be dis-
cussed under cardioproteomics.
The cellular and molecular mechanisms underlying cardiovascular dysfunctions
are mostly unknown. Molecular cardiology, as a part of molecular medicine,
involves the use of new biotechnology tools to gain an understanding of the cardio-
vascular function and the pathways involved in disease. This provides the founda-
tion for rational and innovative approaches to cardiovascular therapeutics.