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Aorta remodeling responses to distinct atherogenic stimuli: hypertension, hypercholesterolemia and turbulent flow/low wall shear stress.

Prado CM, Rossi MA - Open Cardiovasc Med J (2008)

Bottom Line: This review is based on recently published data from our laboratory.We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet.Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-beta expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, S.P., Brazil.

ABSTRACT
This review is based on recently published data from our laboratory. We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet. Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-beta expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry. Representative views of the aortas from sham-operated rats (A), prestenotic (B) and poststenotic (C) segments from operated rats and sham-operated+HD (D), prestenotic (E) and poststenotic (F) segments from operated+HD. The graph represents the quali-quantitative evaluation of the 3-nitrotyrosine immunoreactivity grade. The analysis revealed an increased expression of 3-nitrotyrosine in endothelial cells and smooth muscle cells in the prestenotic segment from operated group, sham-operated+HD, prestenosis+HD and poststenosis+HD as compared to sham-operated group. Scale bars, 50 µ m.
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Figure 5: Immunohistochemistry. Representative views of the aortas from sham-operated rats (A), prestenotic (B) and poststenotic (C) segments from operated rats and sham-operated+HD (D), prestenotic (E) and poststenotic (F) segments from operated+HD. The graph represents the quali-quantitative evaluation of the 3-nitrotyrosine immunoreactivity grade. The analysis revealed an increased expression of 3-nitrotyrosine in endothelial cells and smooth muscle cells in the prestenotic segment from operated group, sham-operated+HD, prestenosis+HD and poststenosis+HD as compared to sham-operated group. Scale bars, 50 µ m.

Mentions: The analysis revealed an increased expression of eNOS, iNOS (data not shown), and nitrotyrosine in endothelial cells and smooth muscle cells in the prestenotic segment from operated group (Fig. 5B) as compared to sham-operated group (Fig. 5A) and poststenotic segment (Fig. 5C). It is likely that endothelial cell respond to hypertensive stress with augmentation of eNOS and iNOS expression as a compensatory mechanism aiming to increase production of nitric oxide (NO). In a similar model, marked upregulation of eNOS in the aortic segment proximal to coarctation compared with the corresponding segments in sham-operated control was found [25]. It has been suggested that NO production in large amounts by iNOS is a toxic-damaging agent [26], whereas eNOS is a protective enzyme [27]. The increased presence of NT in endothelial cells and, mainly, smooth muscle cells, as compared with the absence or discrete expression of NT in sham-operated indicates an increased production of NO and superoxide that interact to produce peroxynitrite, a powerful oxidant causing damage to multiple cell components including proteins [28]. The significant accumulation of NT, which is the footprint of NO oxidation/inactivation by reactive oxygen species [29], supports the supposition of endothelial dysfunction in the face of marked upregulation of eNOS and iNOS in this model, consistent with avid NO inactivation by oxidative stress in the affected vascular bed. This finding agrees with previous study showing marked increase in NT expression in the aortic segment proximal to constriction above the renal arteries [25]. An increased expression of eNOS in endothelial cells was detected in sham-operated+HD, prestenotic and poststenotic segment from operated+HD as compared with sham-operated group (data not shown). In addition, an increased expression of NT in endothelial cells and smooth muscle cells was detected in sham-operated+HD (Fig. 5D), prestenotic (Fig. 5E) and more markedly in the poststenotic segment (Fig. 5F) from operated+HD as compared with sham-operated group. It has been demonstrated that in the presence of hypercholesterolemia, eNOS generates superoxide and the endothelium acts as a source of reactive oxygen species contributing to the early atherosclerotic process [30-33]. Hypercholesterolemia has been demonstrated to strikingly increase the expression of NT in endothelium, smooth muscle layers and adventitia of the aorta in rabbits [34]. The even more pronounced expression on NT in the poststenotic segments is very likely due to an additional factor, hemodynamic alterations. This assumption is supported by recent study on human coronary arteries showing that NT is present in arterial regions exposed to oscillatory shear stress (curvatures and bifurcations), but not in arterial regions exposed to pulsatile shear stress (straight segments) [35]. The accumulation of NT supports the supposition of endothelial cell dysfunction elicited by hypercholesterolemia. Although NT is considered an emergent inflammatory marker for atherosclerosis [36], the mechanism by which peroxynitrite formation contributes to atherogenesis remains uncertain.


Aorta remodeling responses to distinct atherogenic stimuli: hypertension, hypercholesterolemia and turbulent flow/low wall shear stress.

Prado CM, Rossi MA - Open Cardiovasc Med J (2008)

Immunohistochemistry. Representative views of the aortas from sham-operated rats (A), prestenotic (B) and poststenotic (C) segments from operated rats and sham-operated+HD (D), prestenotic (E) and poststenotic (F) segments from operated+HD. The graph represents the quali-quantitative evaluation of the 3-nitrotyrosine immunoreactivity grade. The analysis revealed an increased expression of 3-nitrotyrosine in endothelial cells and smooth muscle cells in the prestenotic segment from operated group, sham-operated+HD, prestenosis+HD and poststenosis+HD as compared to sham-operated group. Scale bars, 50 µ m.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2570580&req=5

Figure 5: Immunohistochemistry. Representative views of the aortas from sham-operated rats (A), prestenotic (B) and poststenotic (C) segments from operated rats and sham-operated+HD (D), prestenotic (E) and poststenotic (F) segments from operated+HD. The graph represents the quali-quantitative evaluation of the 3-nitrotyrosine immunoreactivity grade. The analysis revealed an increased expression of 3-nitrotyrosine in endothelial cells and smooth muscle cells in the prestenotic segment from operated group, sham-operated+HD, prestenosis+HD and poststenosis+HD as compared to sham-operated group. Scale bars, 50 µ m.
Mentions: The analysis revealed an increased expression of eNOS, iNOS (data not shown), and nitrotyrosine in endothelial cells and smooth muscle cells in the prestenotic segment from operated group (Fig. 5B) as compared to sham-operated group (Fig. 5A) and poststenotic segment (Fig. 5C). It is likely that endothelial cell respond to hypertensive stress with augmentation of eNOS and iNOS expression as a compensatory mechanism aiming to increase production of nitric oxide (NO). In a similar model, marked upregulation of eNOS in the aortic segment proximal to coarctation compared with the corresponding segments in sham-operated control was found [25]. It has been suggested that NO production in large amounts by iNOS is a toxic-damaging agent [26], whereas eNOS is a protective enzyme [27]. The increased presence of NT in endothelial cells and, mainly, smooth muscle cells, as compared with the absence or discrete expression of NT in sham-operated indicates an increased production of NO and superoxide that interact to produce peroxynitrite, a powerful oxidant causing damage to multiple cell components including proteins [28]. The significant accumulation of NT, which is the footprint of NO oxidation/inactivation by reactive oxygen species [29], supports the supposition of endothelial dysfunction in the face of marked upregulation of eNOS and iNOS in this model, consistent with avid NO inactivation by oxidative stress in the affected vascular bed. This finding agrees with previous study showing marked increase in NT expression in the aortic segment proximal to constriction above the renal arteries [25]. An increased expression of eNOS in endothelial cells was detected in sham-operated+HD, prestenotic and poststenotic segment from operated+HD as compared with sham-operated group (data not shown). In addition, an increased expression of NT in endothelial cells and smooth muscle cells was detected in sham-operated+HD (Fig. 5D), prestenotic (Fig. 5E) and more markedly in the poststenotic segment (Fig. 5F) from operated+HD as compared with sham-operated group. It has been demonstrated that in the presence of hypercholesterolemia, eNOS generates superoxide and the endothelium acts as a source of reactive oxygen species contributing to the early atherosclerotic process [30-33]. Hypercholesterolemia has been demonstrated to strikingly increase the expression of NT in endothelium, smooth muscle layers and adventitia of the aorta in rabbits [34]. The even more pronounced expression on NT in the poststenotic segments is very likely due to an additional factor, hemodynamic alterations. This assumption is supported by recent study on human coronary arteries showing that NT is present in arterial regions exposed to oscillatory shear stress (curvatures and bifurcations), but not in arterial regions exposed to pulsatile shear stress (straight segments) [35]. The accumulation of NT supports the supposition of endothelial cell dysfunction elicited by hypercholesterolemia. Although NT is considered an emergent inflammatory marker for atherosclerosis [36], the mechanism by which peroxynitrite formation contributes to atherogenesis remains uncertain.

Bottom Line: This review is based on recently published data from our laboratory.We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet.Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-beta expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, S.P., Brazil.

ABSTRACT
This review is based on recently published data from our laboratory. We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet. Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-beta expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.

No MeSH data available.


Related in: MedlinePlus