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Local oxidative and nitrosative stress increases in the microcirculation during leukocytes-endothelial cell interactions.

Kar S, Kavdia M - PLoS ONE (2012)

Bottom Line: Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability.The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions.The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States of America. s.kar@wayne.edu

ABSTRACT
Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O(2)(•-) and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O(2)(•-) and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O(2)(•-) and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen. The increased O(2) (•-) and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O(2)(•-) in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events.

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Related in: MedlinePlus

Geometrical description of the problem.Panel A shows the schematic of the arteriolar geometry. The geometry consists of concentric cylinders representing the different regions of the arteriole. The different regions fall under the category of either luminal or abluminal region. The luminal and abluminal regions are separated by the endothelial region (E). The luminal region consists of the RBC rich core (CR) and RBC free plasma region (CF). The abluminal region consists of the interstitial region (IS), smooth muscle region (SM), non-perfused (NPT) and capillary perfused (PT) parenchymal regions. L1, L2 and L3 represent the leukocytes interacting with the endothelium. Pin and Pout represent the inlet and outlet of the arteriolar/vessel segment, respectively. P1 and P2 represent the locations where the radial concentration profiles of NO, O2•− and peroxynitrite were obtained and are located at distances of 230 and 345 µm, respectively from Pin. Panel B shows the schematic of finite element mesh grid with relative accuracy set to 0.001.
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pone-0038912-g002: Geometrical description of the problem.Panel A shows the schematic of the arteriolar geometry. The geometry consists of concentric cylinders representing the different regions of the arteriole. The different regions fall under the category of either luminal or abluminal region. The luminal and abluminal regions are separated by the endothelial region (E). The luminal region consists of the RBC rich core (CR) and RBC free plasma region (CF). The abluminal region consists of the interstitial region (IS), smooth muscle region (SM), non-perfused (NPT) and capillary perfused (PT) parenchymal regions. L1, L2 and L3 represent the leukocytes interacting with the endothelium. Pin and Pout represent the inlet and outlet of the arteriolar/vessel segment, respectively. P1 and P2 represent the locations where the radial concentration profiles of NO, O2•− and peroxynitrite were obtained and are located at distances of 230 and 345 µm, respectively from Pin. Panel B shows the schematic of finite element mesh grid with relative accuracy set to 0.001.

Mentions: A cylindrical geometry with concentric cylinders was used to represent the arteriole and its associated regions as shown in Figure 2. These regions include the luminal RBC (red blood cell) rich region (CR), RBC free region next to the vessel wall (CF), endothelium (E), interstitial space (IS) between the endothelium and smooth muscle cells, smooth muscle layer (SM), non-perfused parenchymal tissue (NPT) and perfused parenchymal tissue (PT) region. The CR region in the lumen of the arteriole was considered to have a homogenous solution of RBC’s [34]. The thickness of these different regions is shown in Table 1. Three leukocytes were positioned on the luminal side of the endothelium for all the cases simulated and were named as L1, L2 and L3, respectively. Details about the leukocyte geometry and positioning of the leukocytes are described in the “Model Parameters” subsection.


Local oxidative and nitrosative stress increases in the microcirculation during leukocytes-endothelial cell interactions.

Kar S, Kavdia M - PLoS ONE (2012)

Geometrical description of the problem.Panel A shows the schematic of the arteriolar geometry. The geometry consists of concentric cylinders representing the different regions of the arteriole. The different regions fall under the category of either luminal or abluminal region. The luminal and abluminal regions are separated by the endothelial region (E). The luminal region consists of the RBC rich core (CR) and RBC free plasma region (CF). The abluminal region consists of the interstitial region (IS), smooth muscle region (SM), non-perfused (NPT) and capillary perfused (PT) parenchymal regions. L1, L2 and L3 represent the leukocytes interacting with the endothelium. Pin and Pout represent the inlet and outlet of the arteriolar/vessel segment, respectively. P1 and P2 represent the locations where the radial concentration profiles of NO, O2•− and peroxynitrite were obtained and are located at distances of 230 and 345 µm, respectively from Pin. Panel B shows the schematic of finite element mesh grid with relative accuracy set to 0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375306&req=5

pone-0038912-g002: Geometrical description of the problem.Panel A shows the schematic of the arteriolar geometry. The geometry consists of concentric cylinders representing the different regions of the arteriole. The different regions fall under the category of either luminal or abluminal region. The luminal and abluminal regions are separated by the endothelial region (E). The luminal region consists of the RBC rich core (CR) and RBC free plasma region (CF). The abluminal region consists of the interstitial region (IS), smooth muscle region (SM), non-perfused (NPT) and capillary perfused (PT) parenchymal regions. L1, L2 and L3 represent the leukocytes interacting with the endothelium. Pin and Pout represent the inlet and outlet of the arteriolar/vessel segment, respectively. P1 and P2 represent the locations where the radial concentration profiles of NO, O2•− and peroxynitrite were obtained and are located at distances of 230 and 345 µm, respectively from Pin. Panel B shows the schematic of finite element mesh grid with relative accuracy set to 0.001.
Mentions: A cylindrical geometry with concentric cylinders was used to represent the arteriole and its associated regions as shown in Figure 2. These regions include the luminal RBC (red blood cell) rich region (CR), RBC free region next to the vessel wall (CF), endothelium (E), interstitial space (IS) between the endothelium and smooth muscle cells, smooth muscle layer (SM), non-perfused parenchymal tissue (NPT) and perfused parenchymal tissue (PT) region. The CR region in the lumen of the arteriole was considered to have a homogenous solution of RBC’s [34]. The thickness of these different regions is shown in Table 1. Three leukocytes were positioned on the luminal side of the endothelium for all the cases simulated and were named as L1, L2 and L3, respectively. Details about the leukocyte geometry and positioning of the leukocytes are described in the “Model Parameters” subsection.

Bottom Line: Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability.The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions.The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States of America. s.kar@wayne.edu

ABSTRACT
Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O(2) (•-)) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O(2)(•-) and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O(2)(•-) and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O(2)(•-) and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ~0.6 fold, O(2)(•-) increased ~27 fold and peroxynitrite increased ~30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase in O(2)(•-) and peroxynitrite concentration in the lumen. The increased O(2) (•-) and peroxynitrite can cause leukocytes priming through peroxynitrite and leukocytes activation through secondary stimuli of O(2)(•-) in bloodstream without endothelial interaction. This finding supports that leukocyte rolling/adhesion and activation are independent events.

Show MeSH
Related in: MedlinePlus