Biomedical Engineering Reference
In-Depth Information
5.1 Introduction
According to the World Heart Organization, more people die annually from car-
diovascular diseases (CVD) than from any other cause, since they represent 29 %
of all deaths. By 2030, almost 23.6 million people will probably die from CVD,
this being the first cause of death, representing 42 % of deaths [
1
]. The major
modifiable risk factors associated with ischemic heart disease (IHD) are tobacco
and alcohol use, hypertension, high cholesterol, obesity, diabetes, and physical
inactivity. Other non-modifiable factors related to CVD include aging, family
history of cardiovascular disease, gender, and ethnic origin.
IHD develops when deposits of cholesterol particles accumulate on the walls of
heart blood vessels. These deposits, called plaques, narrow or block the arteries
that supply blood to the heart. Myocardial infarction occurs when, due to lack of
blood flow, there is not enough oxygen in the myocardium. Over time, damage
becomes irreversible, and is accompanied by cell death and tissue necrosis
(Fig.
5.1
). In heart infarct, after cardiomyocyte death, the heart replaces these
necrotic cells with a fibrotic scar mainly composed of activated fibroblasts and
extracellular matrix components. Although cardiac remodeling is a compensatory
mechanism that initially decreases wall stress and increases cardiac output and
stroke volume, ultimately it becomes a maladaptive response leading to contractile
dysfunction, arrhythmias, and heart failure.
Therapies driven to improve myocardial function in IHD include pharmaco-
logical treatment, percutaneous intervention, and surgery. Most of these are aimed
at minimizing the symptoms and preventing progression of the disease, but are
able neither to regenerate the tissue nor to restore the heart function in a main-
tained form. In fact, the last and only resort for severe cases is heart transplantation
with the concomitant limitations of the donor waiting lists and the need for an
immunosuppressive regimen to prevent rejection, which obviously has its own
significant deleterious side effects. The failure of these therapies to rescue the
damaged heart and the inconvenience of heart transplants have led to the emer-
gence of alternative treatments, including gene (reviewed in [
2
,
3
]), protein
(reviewed in [
4
,
5
]), and stem cell (reviewed in [
6
,
7
]) therapies.
Importantly, these new approaches have gone a step further, aiming not only at
the protection but also the regeneration of the damaged heart. Thus, overexpres-
sion of key genes or release of angiogenic and survival cytokines/growth factors
could exert a significant therapeutic potential. Also, stem cell therapy has emerged
as an up-and-coming strategy for obtaining new functional myocytes and vascular
cells. This has led to a renewed interest in the main pathways leading to myo-
cardium regeneration and identification of cardiovascular progenitors.
Furthermore, combination of these therapies with tissue engineering (TE) could
boost their benefits, through strategies that could increase cell function, survival, and
cell homing. Thus, cells, biomaterials and/or biologically active molecules could be
applied with the main objective of restoring, maintaining and/or enhancing tissue and
organ function [
8
] gathering engineering, medical, and biological applications.
