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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

AQP1 deficiency reduced myocardial infarct size at 2 days following MI.((a) top) depicts representative images of the heart in situ, with ligation of the left anterior descending coronary artery. ((a) bottom) depicts representative samples of heart slices taken at the mid-papillary muscle level following MI. The perfused myocardium was stained using Evans blue solution, whereas the occluded vasculature remains uncolored. The arrow indicates the ischemic site. (b) The infarct size is expressed as the percentage of the area at risk, AR. The data are expressed as the mean ± SEM (n = 15, *P < 0.001 vs sham. ##P < 0.01 vs AQP1+/+ and AQP3−/− MI mice). (c) Quantitative real-time RT-PCR demonstrating AQP1 expression in cardiac tissue following MI 0 day and day 2. The values are expressed as the mean ± SEM (n = 6, *P < 0.01 vs. day 0).
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f2: AQP1 deficiency reduced myocardial infarct size at 2 days following MI.((a) top) depicts representative images of the heart in situ, with ligation of the left anterior descending coronary artery. ((a) bottom) depicts representative samples of heart slices taken at the mid-papillary muscle level following MI. The perfused myocardium was stained using Evans blue solution, whereas the occluded vasculature remains uncolored. The arrow indicates the ischemic site. (b) The infarct size is expressed as the percentage of the area at risk, AR. The data are expressed as the mean ± SEM (n = 15, *P < 0.001 vs sham. ##P < 0.01 vs AQP1+/+ and AQP3−/− MI mice). (c) Quantitative real-time RT-PCR demonstrating AQP1 expression in cardiac tissue following MI 0 day and day 2. The values are expressed as the mean ± SEM (n = 6, *P < 0.01 vs. day 0).

Mentions: In order to assess the severity of cardiac injury following MI, cardiac infarct size was measured via NBT staining on day 2 following MI in the AQP1+/+ and AQP1−/− mice [Fig. 2(a)]. Compared with the AQP1+/+ mice, the AQP1−/− mice exhibited significantly smaller infarct size [Fig. 2(b)]. Small infarct sizes were also observed in the control group (sham operated mice) compared with the AQP1+/+ and AQP1−/− mice [Fig. 2(b)]. In order to determine if infarct size reduction was a generalized phenomenon in the AQP deficient mice, we also induced MI in AQP3−/− mice and measured myocardial infarct sizes. No differences were observed between the AQP3+/+ and AQP3−/− mice; however, myocardial infarct size was markedly reduced in the AQP1−/− mice compared with the AQP3−/− mice [Fig. 2(b)]. Figure 2(c) depicts the expression of AQP1 following MI, as said expression was up-regulated compared with before MI. These findings suggest that compensatory upregulation of the other AQPs exerted protective effects in the AQP1−/− mice. We also analyzed the expression of the other AQPs following MI via RT- PCR. However, none of the other AQPs expression levels was up-regulated in the AQP1−/− mice (data not shown). These results are indicative of the involvement of AQP1 in both the pathophysiology and the impairments that occur following MI.


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)

AQP1 deficiency reduced myocardial infarct size at 2 days following MI.((a) top) depicts representative images of the heart in situ, with ligation of the left anterior descending coronary artery. ((a) bottom) depicts representative samples of heart slices taken at the mid-papillary muscle level following MI. The perfused myocardium was stained using Evans blue solution, whereas the occluded vasculature remains uncolored. The arrow indicates the ischemic site. (b) The infarct size is expressed as the percentage of the area at risk, AR. The data are expressed as the mean ± SEM (n = 15, *P < 0.001 vs sham. ##P < 0.01 vs AQP1+/+ and AQP3−/− MI mice). (c) Quantitative real-time RT-PCR demonstrating AQP1 expression in cardiac tissue following MI 0 day and day 2. The values are expressed as the mean ± SEM (n = 6, *P < 0.01 vs. day 0).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562302&req=5

f2: AQP1 deficiency reduced myocardial infarct size at 2 days following MI.((a) top) depicts representative images of the heart in situ, with ligation of the left anterior descending coronary artery. ((a) bottom) depicts representative samples of heart slices taken at the mid-papillary muscle level following MI. The perfused myocardium was stained using Evans blue solution, whereas the occluded vasculature remains uncolored. The arrow indicates the ischemic site. (b) The infarct size is expressed as the percentage of the area at risk, AR. The data are expressed as the mean ± SEM (n = 15, *P < 0.001 vs sham. ##P < 0.01 vs AQP1+/+ and AQP3−/− MI mice). (c) Quantitative real-time RT-PCR demonstrating AQP1 expression in cardiac tissue following MI 0 day and day 2. The values are expressed as the mean ± SEM (n = 6, *P < 0.01 vs. day 0).
Mentions: In order to assess the severity of cardiac injury following MI, cardiac infarct size was measured via NBT staining on day 2 following MI in the AQP1+/+ and AQP1−/− mice [Fig. 2(a)]. Compared with the AQP1+/+ mice, the AQP1−/− mice exhibited significantly smaller infarct size [Fig. 2(b)]. Small infarct sizes were also observed in the control group (sham operated mice) compared with the AQP1+/+ and AQP1−/− mice [Fig. 2(b)]. In order to determine if infarct size reduction was a generalized phenomenon in the AQP deficient mice, we also induced MI in AQP3−/− mice and measured myocardial infarct sizes. No differences were observed between the AQP3+/+ and AQP3−/− mice; however, myocardial infarct size was markedly reduced in the AQP1−/− mice compared with the AQP3−/− mice [Fig. 2(b)]. Figure 2(c) depicts the expression of AQP1 following MI, as said expression was up-regulated compared with before MI. These findings suggest that compensatory upregulation of the other AQPs exerted protective effects in the AQP1−/− mice. We also analyzed the expression of the other AQPs following MI via RT- PCR. However, none of the other AQPs expression levels was up-regulated in the AQP1−/− mice (data not shown). These results are indicative of the involvement of AQP1 in both the pathophysiology and the impairments that occur following MI.

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