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Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

Westergren HU, Grönros J, Heinonen SE, Miliotis T, Jennbacken K, Sabirsh A, Ericsson A, Jönsson-Rylander AC, Svedlund S, Gan LM - PLoS ONE (2015)

Bottom Line: Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity.Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

ABSTRACT

Background: Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob) mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.

Methods and results: In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.

Conclusion: In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

Increased renal pulsatility index and resistivity index in ob/ob mice at 21 weeks of age.Renal flow velocity was measured in lean (n = 11) and leptin-deficient (ob/ob, n = 10) mice at 21 weeks of age using the ultrasound color Doppler technique. A: Renal pulsatility index, B: Renal resistivity index. Values are presented as individual datapoints and means. Statistical analysis was performed using Mann-Whitney U-test and a p-value of less than 0.05 was considered significant.
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pone.0130648.g004: Increased renal pulsatility index and resistivity index in ob/ob mice at 21 weeks of age.Renal flow velocity was measured in lean (n = 11) and leptin-deficient (ob/ob, n = 10) mice at 21 weeks of age using the ultrasound color Doppler technique. A: Renal pulsatility index, B: Renal resistivity index. Values are presented as individual datapoints and means. Statistical analysis was performed using Mann-Whitney U-test and a p-value of less than 0.05 was considered significant.

Mentions: To non-invasively measure renal vascular resistance, we applied a Doppler-guided imaging protocol where PI and RI were used. The ob/ob mice displayed increased mean PI values (1.50±0.13 and 1.18±0.19, respectively) as well as increased mean RI values (0.81±0.04 and 0.69±0.06, respectively) when compared to lean mice (Fig 4).


Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

Westergren HU, Grönros J, Heinonen SE, Miliotis T, Jennbacken K, Sabirsh A, Ericsson A, Jönsson-Rylander AC, Svedlund S, Gan LM - PLoS ONE (2015)

Increased renal pulsatility index and resistivity index in ob/ob mice at 21 weeks of age.Renal flow velocity was measured in lean (n = 11) and leptin-deficient (ob/ob, n = 10) mice at 21 weeks of age using the ultrasound color Doppler technique. A: Renal pulsatility index, B: Renal resistivity index. Values are presented as individual datapoints and means. Statistical analysis was performed using Mann-Whitney U-test and a p-value of less than 0.05 was considered significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476758&req=5

pone.0130648.g004: Increased renal pulsatility index and resistivity index in ob/ob mice at 21 weeks of age.Renal flow velocity was measured in lean (n = 11) and leptin-deficient (ob/ob, n = 10) mice at 21 weeks of age using the ultrasound color Doppler technique. A: Renal pulsatility index, B: Renal resistivity index. Values are presented as individual datapoints and means. Statistical analysis was performed using Mann-Whitney U-test and a p-value of less than 0.05 was considered significant.
Mentions: To non-invasively measure renal vascular resistance, we applied a Doppler-guided imaging protocol where PI and RI were used. The ob/ob mice displayed increased mean PI values (1.50±0.13 and 1.18±0.19, respectively) as well as increased mean RI values (0.81±0.04 and 0.69±0.06, respectively) when compared to lean mice (Fig 4).

Bottom Line: Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity.Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.

ABSTRACT

Background: Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob) mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.

Methods and results: In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.

Conclusion: In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus