8 research outputs found
Medial and adventitial macrophages are associated with expansive atherosclerotic remodeling in rabbit femoral artery
Expansive vascular remodeling is considered
a feature of vulnerable plaques. Although inflammation
is upregulated in the media and adventitia of
atherosclerotic lesions, its contribution to expansive
remodeling is unclear. We investigated this issue in
injured femoral arteries of normo- and hyperlipidemic
rabbits fed with a conventional (CD group; n=20) or a
0.5% cholesterol (ChD group; n=20) diet. Four weeks
after balloon injury of the femoral arteries, we examined
vascular wall alterations, localization of macrophages
and matrix metalloproteases (MMP)-1, -2, -9, and
extracellular matrix. Neointimal formation with luminal
stenosis was evident in both groups, while expansive
remodeling was observed only in the ChD group. Areas
immunopositive for macrophages, MMP-1, -2 and -9
were larger not only in the neointima, but also in the
media and/or adventitia in the injured arterial walls of
the ChD, than in the CD group. Areas containing smooth
muscle cells (SMCs), elastin and collagen were smaller
in the injured arterial walls of the ChD group. MMP-1,
-2 and -9 were mainly localized in infiltrating
macrophages. MMP-2 was also found in SMCs and
adventitial fibroblasts. Vasa vasorum density was significantly increased in injured arteries of ChD group
than in those of CD group. These results suggest that
macrophages in the media and adventitia play an
important role in expansive atherosclerotic remodeling
via extracellular matrix degradation and SMC reduction
Vascular smooth muscle cell expression of ectonucleotidase CD39 (ENTPD1) is required for neointimal formation in mice
Vascular smooth muscle cell (VSMC) migration and proliferation are critical steps in the pathogenesis of atherosclerosis, post-angioplasty restenosis, neointimal hyperplasia, and chronic allograft rejection. Extracellular nucleotides are known to influence both migration and proliferation of VSMC. Although it is well established that vascular endothelial Cd39/ENTPD1 regulates blood nucleotide concentrations, whether Cd39 associated with VSMC also impacts vascular wall pathology has not been investigated. The objective of this paper is to determine levels of expression of Cd39 on VSMC and functional consequences of gene deletion in vitro and in vivo. Cd39 is the major ectonucleotidase in VSMC, as shown by substantive decreases in ecto-ATPase and -ADPase activity in Cd39-null cells compared to wild type. Significant decreases in neointimal lesion formation are observed in Cd39-null mice at 21Â days post arterial balloon injury. Stimulated Cd39-null VSMC have pronounced proliferative responses in vitro. However, using Transwell systems, we show that Cd39-null VSMC fail to migrate in response to ATP, UTP, and PDGF. Cd39 is the dominant ectonucleotidase expressed by VSMC. Deletion of Cd39 in mice results in decreased neointimal formation after vascular injury and is associated with impaired VSMC migration responses in vitro
High Signal Intensity on Diffusion-Weighted Images Reflects Acute Phase of Deep Vein Thrombus
Physiological level of norepinephrine increases adenine nucleotides hydrolysis in rat blood serum
Extracellular adenosine 5′-triphosphate (ATP) and its breakdown products, adenosine 5′-diphosphate (ADP) and adenosine, have significant effects on a variety of biological processes. NTPDase enzymes, responsible for adenine nucleotides hydrolysis, are considered the major regulators of purinergic signaling in the blood. Previous work by our group demonstrated that ATP and ADP hydrolysis in rat blood serum are higher during the dark (activity) phase compared to the light (rest) phase. In nocturnal animals (e.g., rats), important physiological changes occur during the dark phase, such as increased circulating levels of melatonin, corticosterone, and norepinephrine (NE). This study investigated the physiological effects, in vivo and in vitro, of melatonin, dexamethasone, and NE upon nucleotides hydrolysis in rat blood serum. For in vivo experiments, the animals received a single injection of saline (control), melatonin (0.05 mg/kg), dexamethasone (0.1 mg/kg), or NE (0.03 mg/kg). For in vitro experiments, melatonin (1.0 nM), dexamethasone (1.0 μM), or NE (1.0 nM) was added directly to the reaction medium with blood serum before starting the enzyme assay. The results demonstrated that ATP and ADP hydrolysis in both in vitro and in vivo experiments were significantly higher with NE treatment compared to control (in vitro: ATP = 36.63%, ADP = 22.43%, P < 0.05; in vivo: ATP = 44.1%, ADP = 37.28%, P < 0.001). No significant differences in adenine nucleotides hydrolysis were observed with melatonin and dexamethasone treatments. This study suggests a modulatory role of NE in the nucleotidases pathway, decreasing extracellular ATP and ADP, and suggests that NE might modulate its own release by increasing the activities of soluble nucleotidases