Biomedical Engineering Reference
In-Depth Information
been synthesized and studied.
3,4
Nowadays, the family of carbonaceous nanomaterials has expanded
from fullerenes to nanotubes and graphene.
12.2.1.1 Carbon Nanotubes
Carbon nanotubes (CNTs) represent a novel class of nanomaterials and have drawn ever-increas-
ing attention to the nanomedicine arena. CNTs exist in two forms, single-wall carbon nanotubes
(SWCNTs) and multiwall carbon nanotubes (MWCNTs). To date, systemic endpoint effects, includ-
ing effects on the cardiovascular systems following pulmonary CNTs exposure, have been observed
in several studies. A number of systemic markers and indicators were recorded to evaluate the
cardiovascular toxicity of CNTs. Furthermore, the possible mechanisms have also been investigated
accordingly.
Early in 2005, the dose-dependent damage to mitochondrial DNA (deoxyribonucleic acid) in
the aortas of mice was observed at 7, 28, and 60 days after pharyngeal aspiration CNT treatment.
5,6
It was concluded that these oxidative changes resulted from the altered expression of inflamma-
tory genes, including intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemotactic
protein-1 (MCP-1) in the heart. The authors further studied the effects of CNTs on the heart by
pharyngeally instilling a total dose of 20 μg SWCNTs into hypercholesterolemic (ApoE
−/−
) mice.
6,7
At the end of the exposure regiment, the percent of the aortic area covered by plaque was signifi-
cantly increased in the CNT-treated mice compared to the vehicle-treated controls. A morphometric
analysis revealed a significant increase in atherosclerotic lesions in the brachiocephalic arteries
of the CNT-treated mice. The authors concluded that the effects in the heart might be caused by
cytokines released from inflamed areas in the lungs and/or by CNTs that leave the lungs and enter
systemic circulation.
5,7
Erdely et al.
8
observed generalized stress responses in various extrapulmonary tissues, includ-
ing acute sensitivity in the aorta within 4 h of CNT pharyngeal aspiration. Furthermore, MWCNTs
produced a greater magnitude response than SWCNTs at an equal mass dose.
8
Therefore, they pri-
marily focused on MWCNTs in a further study where elevated levels of serum interleukin-6 (IL-6)
and the tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) in the aortas were found in mice
with pulmonary exposure to CNTs.
9
The former was reported to be an indicator of vascular dys-
function and prothrombotic potential,
10
and the latter was proposed to be a systemic marker for vas-
cular inflammation.11
11
A key mechanism proposed for the contribution of these downstream effects
observed in CNT exposure is the release of soluble mediators from the lung into circulation.
8,12
It
was also found that the lung's response was translocated to the periphery via the blood following
pulmonary exposure to CNTs.
9
A more recent study monitored the arterial baroreflex control of the sinus node as an index of
cardiovascular autonomic control after pulmonary exposure to SWCNTs.
13
A significant decrease
in the number of baroreflex sequences (from 502 at baseline to 194 after 4 weeks) was observed
in SWCNT-instilled rats, whereas no significant change was detected in controls, suggesting that
SWCNTs may affect autonomic cardiovascular control regulation.
Wingard and coworkers
14
demonstrated that MWCNT instillation in C57BL/6 mice resulted
in the exacerbation of cardiac ischemia/reperfusion (IR) injuries in a dose-dependent manner at
1 day postexposure. Further mechanistic studies performed in the same laboratory revealed that
MWCNTs activated mast cells through the IL-33/ST2 axis, altered pulmonary function, and exac-
erbated IR injury responses in the heart.
15
The adverse health effects of CNTs are usually studied by intratracheal inhalation or instil-
lation because pulmonary exposure is the major route for these lightweight fibrous materials to
affect human health during their production and application. Recently, the field of CNT applica-
tion is expanding to biomedical research where intravenous (IV) injections are a frequently used
administration route. A number of studies have examined the effects of CNTs on the cardiovascular
system upon IV injections. The accumulation of CNTs in the heart upon IV injection was rela-
tively low; thus, it is often not discussed in the literatures.
16,17
The above fact also explains the low
