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Aquaporin-1 Deficiency Protects Against Myocardial Infarction by Reducing Both Edema and Apoptosis in Mice.

Li L, Weng Z, Yao C, Song Y, Ma T - Sci Rep (2015)

Bottom Line: Under physiological conditions, AQP1-/- mice develop normally; however, in the setting of MI, they exhibit cardioprotective properties, as shown by reduced cardiac infarct size determined via NBT staining, improved cardiac function determined via left ventricular catheter measurements, decreased AQP1-dependent myocardial edema determined via water content assays, and decreased apoptosis determined via TUNEL analysis.AQP1 deficiency protected cardiac function from ischemic injury following MI.Furthermore, AQP1 deficiency reduced microvascular permeability via the stabilization of HIF-1α levels in endothelial cells and decreased cellular apoptosis following MI.

View Article: PubMed Central - PubMed

Affiliation: Liaoning Medical University, Department of Cell Biology, Jinzhou, PR China.

ABSTRACT
Many studies have determined that AQP1 plays an important role in edema formation and resolution in various tissues via water transport across the cell membrane. The aim of this research was to determine both if and how AQP1 is associated with cardiac ischemic injury, particularly the development of edema following myocardial infarction (MI). AQP1+/+ and AQP1-/- mice were used to create the MI model. Under physiological conditions, AQP1-/- mice develop normally; however, in the setting of MI, they exhibit cardioprotective properties, as shown by reduced cardiac infarct size determined via NBT staining, improved cardiac function determined via left ventricular catheter measurements, decreased AQP1-dependent myocardial edema determined via water content assays, and decreased apoptosis determined via TUNEL analysis. Cardiac ischemia caused by hypoxia secondary to AQP1 deficiency stabilized the expression of HIF-1α in endothelial cells and subsequently decreased microvascular permeability, resulting in the development of edema. The AQP1-dependent myocardial edema and apoptosis contributed to the development of MI. AQP1 deficiency protected cardiac function from ischemic injury following MI. Furthermore, AQP1 deficiency reduced microvascular permeability via the stabilization of HIF-1α levels in endothelial cells and decreased cellular apoptosis following MI.

No MeSH data available.


Related in: MedlinePlus

The effects of AQP1 deficiency on myocardial edema following MI.(a) Myocardial interstitial edema was observed via H&E staining in the AQP1+/+ (left) and AQP1−/− mice (right) at 18 h following MI. Scale bar: 100 μm. (b) A quantitative analysis of myocardial water content at 0 h, 18 h and 36 h following MI in the AQP1−/− and AQP1+/+ mice using both dry and wet weights. The values are expressed as the mean ± SEM (n = 12, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 18 h and 36 h). (c) A quantitative analysis of microvascular permeability via measurements of FITC-dextran leakage using spectrophotometry (n = 6, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 36 h).
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f4: The effects of AQP1 deficiency on myocardial edema following MI.(a) Myocardial interstitial edema was observed via H&E staining in the AQP1+/+ (left) and AQP1−/− mice (right) at 18 h following MI. Scale bar: 100 μm. (b) A quantitative analysis of myocardial water content at 0 h, 18 h and 36 h following MI in the AQP1−/− and AQP1+/+ mice using both dry and wet weights. The values are expressed as the mean ± SEM (n = 12, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 18 h and 36 h). (c) A quantitative analysis of microvascular permeability via measurements of FITC-dextran leakage using spectrophotometry (n = 6, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 36 h).

Mentions: AQP-facilitated plasma membrane water permeability reportedly promotes the development of edema in a variety of tissues8. In order to determine whether this mechanism is applicable to cardiac tissue, we assessed the development of AQP1-dependent myocardial edema following MI via the following methods: a myocardial water content assay and microvascular permeability assay. We first compared myocardial water content in the AQP1−/− and AQP1+/+ mice at both 18 and 36 h following MI. As demonstrated in Fig. 4(a), MI caused in increase in the water content of the myocardium interstitial space, as determined via H&E staining. The AQP1−/− mice exhibited significant smaller myocardial interstitial spaces compared with the AQP1+/+ mice. Figure 4(b) also depicted similar reductions in the water content of the AQP1−/− MI mice using both the wet and dry weights of the infarct myocardium. The edema peaked at 36 h following MI in the AQP1+/+ mice. The microvascular permeability assay exhibited no significant differences between the AQP1−/− and AQP1+/+ mice secondary to FITC-dextran leakage, at 18 h following MI, as demonstrated in Fig. 4(c). These results support the involvement of AQP1 in the development of myocardial edema following MI. However, at 36 h following MI, FITC-dextran leakage was significantly increased in the AQP1+/+ MI mice compared with the AQP1−/− MI mice. As AQP1−/− mice suffer water loss under stress due to deficient kidney re-absorption, we used AQP3−/− mice in order to avoid water loss. However, no differences were observed in myocardial water content between the AQP3+/+ and AQP3−/− mice (data not shown). These results indicated that increased microvascular permeability exacerbated AQP1-dependent myocardial edema.


Aquaporin-1 Deficiency Protects Against Myocardial Infarction by Reducing Both Edema and Apoptosis in Mice.

Li L, Weng Z, Yao C, Song Y, Ma T - Sci Rep (2015)

The effects of AQP1 deficiency on myocardial edema following MI.(a) Myocardial interstitial edema was observed via H&E staining in the AQP1+/+ (left) and AQP1−/− mice (right) at 18 h following MI. Scale bar: 100 μm. (b) A quantitative analysis of myocardial water content at 0 h, 18 h and 36 h following MI in the AQP1−/− and AQP1+/+ mice using both dry and wet weights. The values are expressed as the mean ± SEM (n = 12, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 18 h and 36 h). (c) A quantitative analysis of microvascular permeability via measurements of FITC-dextran leakage using spectrophotometry (n = 6, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 36 h).
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f4: The effects of AQP1 deficiency on myocardial edema following MI.(a) Myocardial interstitial edema was observed via H&E staining in the AQP1+/+ (left) and AQP1−/− mice (right) at 18 h following MI. Scale bar: 100 μm. (b) A quantitative analysis of myocardial water content at 0 h, 18 h and 36 h following MI in the AQP1−/− and AQP1+/+ mice using both dry and wet weights. The values are expressed as the mean ± SEM (n = 12, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 18 h and 36 h). (c) A quantitative analysis of microvascular permeability via measurements of FITC-dextran leakage using spectrophotometry (n = 6, *P < 0.05, **P < 0.01 vs 0 h. ##P < 0.01 vs AQP1+/+ mice at 36 h).
Mentions: AQP-facilitated plasma membrane water permeability reportedly promotes the development of edema in a variety of tissues8. In order to determine whether this mechanism is applicable to cardiac tissue, we assessed the development of AQP1-dependent myocardial edema following MI via the following methods: a myocardial water content assay and microvascular permeability assay. We first compared myocardial water content in the AQP1−/− and AQP1+/+ mice at both 18 and 36 h following MI. As demonstrated in Fig. 4(a), MI caused in increase in the water content of the myocardium interstitial space, as determined via H&E staining. The AQP1−/− mice exhibited significant smaller myocardial interstitial spaces compared with the AQP1+/+ mice. Figure 4(b) also depicted similar reductions in the water content of the AQP1−/− MI mice using both the wet and dry weights of the infarct myocardium. The edema peaked at 36 h following MI in the AQP1+/+ mice. The microvascular permeability assay exhibited no significant differences between the AQP1−/− and AQP1+/+ mice secondary to FITC-dextran leakage, at 18 h following MI, as demonstrated in Fig. 4(c). These results support the involvement of AQP1 in the development of myocardial edema following MI. However, at 36 h following MI, FITC-dextran leakage was significantly increased in the AQP1+/+ MI mice compared with the AQP1−/− MI mice. As AQP1−/− mice suffer water loss under stress due to deficient kidney re-absorption, we used AQP3−/− mice in order to avoid water loss. However, no differences were observed in myocardial water content between the AQP3+/+ and AQP3−/− mice (data not shown). These results indicated that increased microvascular permeability exacerbated AQP1-dependent myocardial edema.

Bottom Line: Under physiological conditions, AQP1-/- mice develop normally; however, in the setting of MI, they exhibit cardioprotective properties, as shown by reduced cardiac infarct size determined via NBT staining, improved cardiac function determined via left ventricular catheter measurements, decreased AQP1-dependent myocardial edema determined via water content assays, and decreased apoptosis determined via TUNEL analysis.AQP1 deficiency protected cardiac function from ischemic injury following MI.Furthermore, AQP1 deficiency reduced microvascular permeability via the stabilization of HIF-1α levels in endothelial cells and decreased cellular apoptosis following MI.

View Article: PubMed Central - PubMed

Affiliation: Liaoning Medical University, Department of Cell Biology, Jinzhou, PR China.

ABSTRACT
Many studies have determined that AQP1 plays an important role in edema formation and resolution in various tissues via water transport across the cell membrane. The aim of this research was to determine both if and how AQP1 is associated with cardiac ischemic injury, particularly the development of edema following myocardial infarction (MI). AQP1+/+ and AQP1-/- mice were used to create the MI model. Under physiological conditions, AQP1-/- mice develop normally; however, in the setting of MI, they exhibit cardioprotective properties, as shown by reduced cardiac infarct size determined via NBT staining, improved cardiac function determined via left ventricular catheter measurements, decreased AQP1-dependent myocardial edema determined via water content assays, and decreased apoptosis determined via TUNEL analysis. Cardiac ischemia caused by hypoxia secondary to AQP1 deficiency stabilized the expression of HIF-1α in endothelial cells and subsequently decreased microvascular permeability, resulting in the development of edema. The AQP1-dependent myocardial edema and apoptosis contributed to the development of MI. AQP1 deficiency protected cardiac function from ischemic injury following MI. Furthermore, AQP1 deficiency reduced microvascular permeability via the stabilization of HIF-1α levels in endothelial cells and decreased cellular apoptosis following MI.

No MeSH data available.


Related in: MedlinePlus