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Reactive oxygen species and vascular remodeling in cardiovascular diseases
Figure 2. Types of vascular remodeling. Classification refers to lumen (14, 15). The mechanisms leading to this type of
changes on the lumen diameter (inward: upper row or outward remodeling are poorly known but some authors suggest
lower row) and vessel cross-sectional area (hypotrophic: left that a combination of inward growth and peripheral
column; eutrophic: center column and hypertrophic: right apoptosis or prolonged vasoconstriction of vascular cells
column). Adapted from Mulvany (8). embedded in an expanded ECM can lead to eutrophic
remodeling (9, 16).
- Hypertrophic remodeling is characterized by an
increase in the media thickness, media/lumen and vascular The importance of the vascular structural abnormalities
cross sectional area associated with a more evident in cardiovascular diseases, such as hypertension, lies on
contribution of cell growth (8). This type of remodeling is the fact that in patients it has been demonstrated that the
characteristic of large arteries in ageing or in pathologies media to lumen ratio parameter has a prognostic value of
like hypertension (9) or restenosis which is associated with cardiovascular events in a high-risk population (17, 18).
proliferation and migration of different cells types (7). Thus, the presence of structural alterations in the
microcirculation may be considered an important link
- Hypotrophic remodeling is associated with a between hypertension and ischemic heart disease, heart
decrease in the amount of material (i.e. diminished cross failure, cerebral ischemic attacks, and renal failure (15).
sectional area) around the vessel wall (8). This type of
remodeling may be related to apoptosis processes and/or to Vascular tone and structure are regulated by the
rearrangement of the material in the vessel wall (10). equilibrium between vasodilator- antiproliferative-
Hypotrophic remodeling has been shown in renal afferent antifibrotic factors and vasoconstrictor- proliferative-
arterioles from spontaneously hypertensive rats (SHR) (11) profibrotic factors, which are released in large part, by the
and in mesenteric resistance arteries from ouabain-induced ECs and VSMCs in response to mechanical or chemical
hypertensive animals (12). Moreover, patients with stimuli. The imbalance between these substances leads to
autosomal dominant hyperimmunoglobulin E syndrome the endothelial dysfunction and/or the vascular remodeling
were found to have a high prevalence of hypotrophic observed in cardiovascular diseases. Vascular remodeling
remodeling in carotid arteries with an increased can be induced by dynamic interactions between local
circumferential stress and enhanced susceptibility to growth factors, vasoactive substances and hemodynamic
dilation and aneurysm formation associated to angiotensin stimuli being all important mediators in the vascular
II (AngII) and apolipoprotein E (13). adaptation process. The number of mediators involved in
altered vascular structure is continuously growing;
- Eutrophic remodeling is characterized by a decrease however, to date it is well admitted that AngII, cytokines,
in the outer and lumen diameters and an increase in the prostanoids and ROS have a key role (7).
media thickness and the media/lumen ratio with no change
in the wall cross sectional area (8). It has been suggested 2.3. Cell proliferation and migration
that this type of remodeling is due to rearrangement of the
same amount of wall material around a smaller vessel As mentioned, wall thickening is one of the main
features of many cardiovascular diseases. Depending on
the specific vascular bed and pathology, the cellular and
non-cellular events leading to altered vascular structure
might be different. Thus, hypertension causes arterial
media thickening with or without cell growth, and ECM
deposition in both humans and animal experimental
models; however, atherosclerosis and reaction to injury
such as endothelial denudation or restenosis cause intimal
thickening associated to variable degrees of alterations in
the surrounding ECM (19, 20) (Figure 3). Although it is
known that during vascular remodeling VSMC
proliferation and migration are processes that take place,
their regulation is not exactly known.
@Real Academia Nacional de Farmacia. Spain 131
