Molecular Diagnosis of Cardiovascular Disorders - Applications of Biotechnology in Cardiovascular Therapeutics - page 135

important physiological factors, such as pH, temperature, or oxygenation and carry
therapeutics as well. Several molecular imaging quantification techniques have
been described that include measurement of signal changes, calculation of the area
of contrast enhancement, mapping of relaxation time changes, or direct detection
of contrast agents through multinuclear imaging or spectroscopy (Winter et al.
2010 ). CMR molecular imaging can be used for early detection of therapeutic
response to drugs, localization of ruptured atherosclerotic plaques, stratification of
patients based on disease biomarkers, tissue-specific drug delivery, confirmation
and quantification of end-organ drug uptake, and noninvasive monitoring of disease
recurrence.
Genetic Cardiovascular Disorders
Several cardiovascular diseases have been recognized to have a genetic component;
indeed, a family history of heart disease has always attracted the physician's atten-
tion. In recent years, molecular genetics has contributed to the development of
molecular cardiology, opening up some new pathways to the diagnosis, prevention,
and treatment of some cardiovascular diseases. Genetic approaches have succeeded
in defining the molecular basis of an increasing array of heart diseases, such as
hypertrophic cardiomyopathy and the long-QT syndrome, associated with serious
arrhythmias. Some of the genes that cause cardiovascular diseases are described in
Chap. 9.
Coronary Heart Disease
Coronary heart disease (CHD) is associated with various disturbances in the coro-
nary artery circulation. It may involve stenosis or narrowing with reduced blood
flow or complete occlusion of the coronary artery or arteries, resulting in myocar-
dial infarction. Linkages have been demonstrated between DNA markers and both
risk factors and certain overt CHD. Many of these correlations involve not merely
one gene, however, but entire chromosome regions containing hundreds of genes.
Such vague relationships may not help to establish a diagnosis as required by either
epidemiology or molecular genetics.
Genome-wide screening of affected siblings has now emerged as a promising
route to identifying new genes or confirming the roles of established genes for
CHD. For each tentative new locus, siblings with premature-onset CHD are com-
pared to see whether they prove identical for one or both parental alleles more often
than would be expected from Mendelian segregation. New common polymorphisms
detected in such screening, however, must be proved to be functional before they
can be confirmed as genetic risk factors for CHD.
Development and progression of atherosclerosis involves recruitment and
binding of circulating leukocytes to areas of inflammation within the vascular