Cardiovascular diseases are the most important cause of death and hospitali
sation in industrialised countries. Although pharmacological, interventiona
l and surgical therapy has achieved major progress during the past 25 years
, most therapeutic measures are only transiently effective or require life-
long medication. Molecular cardiology aims at applying molecular biological
methods for both diagnosis and treatment of cardiovascular disease.
With respect to diagnosis of cardiac diseases such as hypertrophic cardiomy
opathy or the long QT syndrome, it has become possible to characterise muta
tions in the genome responsible for the disease process. It is interesting
that different mutations inducing hypertrophic cardiomyopathy are associate
d with a different prognosis and survival time. This example demonstrates t
hat molecular biological analysis allows a better estimation of the individ
ual risk in patients with a monogenetic disease. Such diseases are an impor
tant target for genetic therapies, as transfection of normal copies of the
diseased gene would potentially cure the patient. Clinical experience has s
o far only been obtained in patients with familial hypercholesterolaemia an
d mutations in the LDL receptor.
Molecular biology also permits a better understanding of the pathogenesis o
f atherosclerosis, which is responsible for most cardiovascular disease. At
herosclerosis is a disease of conduit arteries such as the aorta and the co
ronary arteries. In recent years it has become possible to characterise bet
ter the molecular and cellular changes leading to endothelial dysfunction,
coronary vasospasm, adhesion of monocytes and lymphocytes, proliferation an
d migration of vascular smooth muscle cells, and formation of extracellular
matrix. This improved understanding has led to new therapeutic approaches,
although a genetic intervention is not probable for the moment due to the
complexity of the disease process.
Balloon dilatation of coronary arteries has generated a new disease, namely
restenosis. Vascular remodelling and proliferation are of major importance
for this disease. Many cellular mechanisms have been characterised, and ge
ne therapeutic strategies including signal transduction and cell cycle regu
lation have already been investigated experimentally. Coronary bypass graft
disease represents another target for gene therapy in the vascular system.
Many experimental and a few clinical protocols have been performed with th
e saphenous vein. Yet another strategy for gene therapy is the endogenous f
ormation of new vessels due to the effect of vascular endothelial growth fa
ctor.
Molecular cardiology is a new and promising approach to a better understand
ing of cardiovascular disease. Genetic analysis is already established for
the diagnosis of single gene disorders and, in addition, allows a more prec
ise prognostic evaluation Cardiovascular gene therapy has been focussing ma
inly on angiogenesis; other strategies, however, are under investigation ma
inly in an experimental setting.