Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 75

non-communicable diseases such as cancer, diabetes and chronic respira-
tory diseases. Long-term exposure to behavioral risk factors leads to hyper-
tension, increased blood glucose, dyslipidemia and obesity. Lipids are likely
to deposit inside the arteries causing the inner surface of blood vessels to
become irregular, so that it is dicult for blood to flow through, the disease
process known as atherosclerosis. Eventually, fatty plaque can rupture,
causing the formation of a blood clot in the heart resulting in coronary
arterial disease. 2
According to Mendis et al., CVDs can be classified into two groups: (1) those
due to atherosclerosis such as ischemic heart disease or coronary artery dis-
ease, cerebrovascular disease, diseases of the aorta and arteries, including
hypertension and peripheral vascular disease; and (2) other CVDs, such as
congenital heart disease, rheumatic heart disease, cardiomyopathies and
cardiac arrhythmias. Ischemic heart disease and stroke have increased in the
last two decades by 29% and 19%, respectively, with ischemic heart disease
the first cause of disability-adjusted life years in the last regional ranking. 2
When the blood flow to the heart is interrupted due to a ruptured ath-
erosclerotic plaque, the decrease in the supply of oxygen and nutrients can
damage the heart muscle. After the onset of myocardial ischemia histo-
logical cell death can occur and could lead to complete necrosis depending
on the presence of collateral circulation to the ischemic zone, persistent or
intermittent coronary arterial occlusion, the sensitivity of the cardiomyo-
cytes to ischemia and the individual demand for oxygen and nutrients. 3
During post-infarction Collagen fibers decrease in number and in-
flammatory cells infiltrate the necrotic tissue which leads to dilatation and
wall thinning of the infarcted area, an increase in sarcomere length and a
reduction in intercellular space; these changes are known as cardiac re-
modeling. This is a compensatory post-infarction mechanism that initially
decreases wall stress and increases cardiac output and stroke volume. Dur-
ing this process cardiomyocytes suffer modifications in size and shape and
in the molecular mechanisms involved in contraction and relaxation. At
first, these adaptations seem to be beneficial; however, as the ventricle
continues to dilate wall stress increases in the infarcted ventricle. Besides,
matrix protein deposition and scar formation become evident constituting a
maladaptive response leading to contractile dysfunction, arrhythmias and
heart failure (HF). 4-6
Percutaneous coronary intervention practice facilitates rapid relief of
acute occlusion and pharmacological treatment constitutes the standard
therapy but both could lead to HF and a posterior transplant requirement. 5,7
The application of regenerative therapies aim at preserving or restoring lost
myocardial function which promotes long-term survival. These treatments
are based on understanding the intrinsic cardiac repair process in order to
modify inflammation in the ischemic zone, avoid cardiomyocyte apoptosis
or stimulate neovascularization, cell survival, myocardial contraction and
cardiomyogenesis. These novel methods include gene therapy and tissue
engineering that comprises cell therapy and protein therapy. 5

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