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Different Anti-Contractile Function and Nitric Oxide Production of Thoracic and Abdominal Perivascular Adipose Tissues.

Victorio JA, Fontes MT, Rossoni LV, Davel AP - Front Physiol (2016)

Bottom Line: PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta.However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT.In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas Campinas, Brazil.

ABSTRACT
Divergent phenotypes between the perivascular adipose tissue (PVAT) surrounding the abdominal and the thoracic aorta might be implicated in regional aortic differences, such as susceptibility to atherosclerosis. Although PVAT of the thoracic aorta exhibits anti-contractile function, the role of PVAT in the regulation of the vascular tone of the abdominal aorta is not well defined. In the present study, we compared the anti-contractile function, nitric oxide (NO) availability, and reactive oxygen species (ROS) formation in PVAT and vessel walls of abdominal and thoracic aorta. Abdominal and thoracic aortic tissue from male Wistar rats were used to perform functional and molecular experiments. PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta. Abdominal PVAT exhibited a reduction in endothelial NO synthase (eNOS) expression compared with thoracic PVAT, without differences in eNOS expression in the vessel walls. In agreement with this result, NO production evaluated in situ using 4,5-diaminofluorescein was less pronounced in abdominal compared with thoracic aortic PVAT, whereas no significant difference was observed for endothelial NO production. Moreover, NOS inhibition with L-NAME enhanced the phenylephrine-induced contraction in endothelial-denuded rings with PVAT from thoracic but not abdominal aorta. ROS formation and lipid peroxidation products evaluated through the quantification of hydroethidine fluorescence and 4-hydroxynonenal adducts, respectively, were similar between PVAT and vessel walls from the abdominal and thoracic aorta. Extracellular superoxide dismutase (SOD) expression was similar between the vessel walls and PVAT of the abdominal and thoracic aorta. However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT. In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta. Although relative SOD isoforms are different along the aorta, ROS formation, and lipid peroxidation seem to be similar. These findings highlight the specific regional roles of PVAT depots in the control of vascular function that can drive differences in susceptibility to vascular injury.

No MeSH data available.


Related in: MedlinePlus

Reactive oxygen species generation and lipid peroxidation are similar along the aorta. (A) Representative fluorographs (top) and quantified (bottom) DHE fluorescence obtained in transverse sections of vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. DHE fluorescence was evaluated at the basal level and in the presence of the SOD mimetic MnTMPyP. Scale bar = 100 μm (20X objective). Values of the integrated density of hydroethidine-positive (EB-positive) nuclei fluorescence were normalized to nuclei number, which was analyzed by DAPI staining in each sample. (B) Expression of 4-hydroxynonenal (4-HNE) adducts in vessel walls and PVAT from ABD and THO aorta. Representative blots and Ponceau S staining were demonstrated at the right panel and densitometric analysis is expressed as the fold change of THO expression (left panel). Data are expressed as the means ± SEM; the number of animals is indicated in the bars of the graph. Student's t-test.
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Figure 3: Reactive oxygen species generation and lipid peroxidation are similar along the aorta. (A) Representative fluorographs (top) and quantified (bottom) DHE fluorescence obtained in transverse sections of vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. DHE fluorescence was evaluated at the basal level and in the presence of the SOD mimetic MnTMPyP. Scale bar = 100 μm (20X objective). Values of the integrated density of hydroethidine-positive (EB-positive) nuclei fluorescence were normalized to nuclei number, which was analyzed by DAPI staining in each sample. (B) Expression of 4-hydroxynonenal (4-HNE) adducts in vessel walls and PVAT from ABD and THO aorta. Representative blots and Ponceau S staining were demonstrated at the right panel and densitometric analysis is expressed as the fold change of THO expression (left panel). Data are expressed as the means ± SEM; the number of animals is indicated in the bars of the graph. Student's t-test.

Mentions: ROS production was detected based on DHE fluorescence (Figure 3A), and lipid peroxidation was evaluated based on the expression of 4-HNE adducts (Figure 3B). ROS production was almost fully inhibited by MnTMPyP in abdominal and thoracic aorta, suggesting superoxide as the main ROS evaluated in situ by DHE fluorescence in both the vascular wall and PVAT (Figure 3A). Both ROS production and lipid peroxidation were similar in abdominal and thoracic aortic tissues and PVAT (Figures 3A,B).


Different Anti-Contractile Function and Nitric Oxide Production of Thoracic and Abdominal Perivascular Adipose Tissues.

Victorio JA, Fontes MT, Rossoni LV, Davel AP - Front Physiol (2016)

Reactive oxygen species generation and lipid peroxidation are similar along the aorta. (A) Representative fluorographs (top) and quantified (bottom) DHE fluorescence obtained in transverse sections of vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. DHE fluorescence was evaluated at the basal level and in the presence of the SOD mimetic MnTMPyP. Scale bar = 100 μm (20X objective). Values of the integrated density of hydroethidine-positive (EB-positive) nuclei fluorescence were normalized to nuclei number, which was analyzed by DAPI staining in each sample. (B) Expression of 4-hydroxynonenal (4-HNE) adducts in vessel walls and PVAT from ABD and THO aorta. Representative blots and Ponceau S staining were demonstrated at the right panel and densitometric analysis is expressed as the fold change of THO expression (left panel). Data are expressed as the means ± SEM; the number of animals is indicated in the bars of the graph. Student's t-test.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4940415&req=5

Figure 3: Reactive oxygen species generation and lipid peroxidation are similar along the aorta. (A) Representative fluorographs (top) and quantified (bottom) DHE fluorescence obtained in transverse sections of vessel walls and PVAT from thoracic (THO) and abdominal (ABD) aorta. DHE fluorescence was evaluated at the basal level and in the presence of the SOD mimetic MnTMPyP. Scale bar = 100 μm (20X objective). Values of the integrated density of hydroethidine-positive (EB-positive) nuclei fluorescence were normalized to nuclei number, which was analyzed by DAPI staining in each sample. (B) Expression of 4-hydroxynonenal (4-HNE) adducts in vessel walls and PVAT from ABD and THO aorta. Representative blots and Ponceau S staining were demonstrated at the right panel and densitometric analysis is expressed as the fold change of THO expression (left panel). Data are expressed as the means ± SEM; the number of animals is indicated in the bars of the graph. Student's t-test.
Mentions: ROS production was detected based on DHE fluorescence (Figure 3A), and lipid peroxidation was evaluated based on the expression of 4-HNE adducts (Figure 3B). ROS production was almost fully inhibited by MnTMPyP in abdominal and thoracic aorta, suggesting superoxide as the main ROS evaluated in situ by DHE fluorescence in both the vascular wall and PVAT (Figure 3A). Both ROS production and lipid peroxidation were similar in abdominal and thoracic aortic tissues and PVAT (Figures 3A,B).

Bottom Line: PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta.However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT.In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta.

View Article: PubMed Central - PubMed

Affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas Campinas, Brazil.

ABSTRACT
Divergent phenotypes between the perivascular adipose tissue (PVAT) surrounding the abdominal and the thoracic aorta might be implicated in regional aortic differences, such as susceptibility to atherosclerosis. Although PVAT of the thoracic aorta exhibits anti-contractile function, the role of PVAT in the regulation of the vascular tone of the abdominal aorta is not well defined. In the present study, we compared the anti-contractile function, nitric oxide (NO) availability, and reactive oxygen species (ROS) formation in PVAT and vessel walls of abdominal and thoracic aorta. Abdominal and thoracic aortic tissue from male Wistar rats were used to perform functional and molecular experiments. PVAT reduced the contraction evoked by phenylephrine in the absence and presence of endothelium in the thoracic aorta, whereas this anti-contractile effect was not observed in the abdominal aorta. Abdominal PVAT exhibited a reduction in endothelial NO synthase (eNOS) expression compared with thoracic PVAT, without differences in eNOS expression in the vessel walls. In agreement with this result, NO production evaluated in situ using 4,5-diaminofluorescein was less pronounced in abdominal compared with thoracic aortic PVAT, whereas no significant difference was observed for endothelial NO production. Moreover, NOS inhibition with L-NAME enhanced the phenylephrine-induced contraction in endothelial-denuded rings with PVAT from thoracic but not abdominal aorta. ROS formation and lipid peroxidation products evaluated through the quantification of hydroethidine fluorescence and 4-hydroxynonenal adducts, respectively, were similar between PVAT and vessel walls from the abdominal and thoracic aorta. Extracellular superoxide dismutase (SOD) expression was similar between the vessel walls and PVAT of the abdominal and thoracic aorta. However, Mn-SOD levels were reduced, while CuZn-SOD levels were increased in abdominal PVAT compared with thoracic aortic PVAT. In conclusion, our results demonstrate that the anti-contractile function of PVAT is lost in the abdominal portion of the aorta through a reduction in eNOS-derived NO production compared with the thoracic aorta. Although relative SOD isoforms are different along the aorta, ROS formation, and lipid peroxidation seem to be similar. These findings highlight the specific regional roles of PVAT depots in the control of vascular function that can drive differences in susceptibility to vascular injury.

No MeSH data available.


Related in: MedlinePlus