Biology Reference
In-Depth Information
rats, but was lower than in the other tissues analyzed. Overall, these results indicate
that functional P2Y
2
R expression is significantly higher in P2Y
2
R overexpressing
Tg rat tissue, as compared to WT controls.
In the P2Y
2
R overexpressing rat, P2Y
2
R-mediated increases in [Ca
2+
]
i
in aortic
SMCs were 18 times greater than in WT rat aortic SMCs [1]. Similarly, P2Y
2
R
mRNA expression in aorta was 27 times greater in P2Y
2
R overexpressing Tg rats
as compared to WT rats, indicating a close correlation between increased P2Y
2
R
mRNA expression and functional activity, which suggests that these Tg rats will
be ideal for investigations on the role of P2Y
2
R overexpression in vascular lesion
development.
4.2 P2Y
2
Receptors in Angiogenesis
Vascular endothelial cells are involved in a variety of physiological processes,
including vasoregulation, repair of the vascular intima, blood clotting, and devel-
opment of new blood vessels (i.e., angiogenesis). Vascular tone and blood flow can
be regulated by release from endothelium of compounds such as nitric oxide (NO),
prostacyclin (PGI
2
), ATP, and endothelin, whereas endothelial cell proliferation and
migration are important processes required for the continual repair of established
blood vessels [33]. During the formation of new blood vessels, endothelial cells
release enzymes that degrade the basement membrane, enabling some endothe-
lial cells to migrate through the vascular wall and proliferate to create capillaries
that extend perpendicular to the original blood vessel [25]. Angiogenesis occurs
in many physiological and pathophysiological conditions, including development,
wound healing, ovarian and menstrual cycling, rheumatoid arthritis, and tumor
growth.
4.2.1 P2Y
2
Receptors and Neovascularization of Atherosclerotic
Plaques
Neovascularization in atherosclerotic plaques was first noted by Koster [46] more
than 100 years ago. Barger also documented the existence of neovascularization in
atherosclerosis using cineangiography at autopsy [7]. Neovascularization has been
postulated to play a role in atherosclerosis by providing growth factors and cytokines
to regions of plaque growth [42]. The clinical significance of neovascularization in
atherosclerosis is unknown. Accumulating histopathological data associate plaque
angiogenesis with rapid progression of unstable angina [82]. These studies confirm
that intimal neovascularization is a ubiquitous feature of atherosclerosis, correlat-
ing with both histological grade and disease symptoms [82]. Vasa vasorum-derived
microvessels do not extend to the intima of normal arteries, penetrating only the
adventitia and outer media [27]. Diffusion of oxygen and other nutrients is lim-
ited to 100
μ
m from the lumen of the blood vessel, which in normal arteries is
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