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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

Representative color Doppler image for measurement of renal flow velocities.Typical recordings of intrarenal flow velocities measurement in segmental renal arteries were performed with color Doppler ultrasound in lean and leptin-deficient (ob/ob) mice at 21 weeks of age. The pulsatility flow profile was used for measurement of peak systolic velocity (PSV) (red line), mean velocity (MV) (blue line) and lowest diastolic velocity (LDV) (yellow line) for calculation of pulsatility index and resistive index. A: Renal flow velocity profile in lean mice. B: Renal flow velocity profile in ob/ob mice.
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pone.0130648.g002: Representative color Doppler image for measurement of renal flow velocities.Typical recordings of intrarenal flow velocities measurement in segmental renal arteries were performed with color Doppler ultrasound in lean and leptin-deficient (ob/ob) mice at 21 weeks of age. The pulsatility flow profile was used for measurement of peak systolic velocity (PSV) (red line), mean velocity (MV) (blue line) and lowest diastolic velocity (LDV) (yellow line) for calculation of pulsatility index and resistive index. A: Renal flow velocity profile in lean mice. B: Renal flow velocity profile in ob/ob mice.

Mentions: Ultrasound examination of the right kidney was performed at 21 weeks of age in combination with the cardiac echocardiography investigation. Standard B-mode examination of the kidney was performed in a long-axis view using the same ultrasound imaging system as described above. Following color-Doppler mapping of the renal vascular tree using a color-Doppler frequency of 32 MHz, a cursor was placed at the central segmental artery and renal flow velocity was measured using pulse wave Doppler (Fig 2). Kidney length was measured off-line at standard B-mode long axis view, blinded to the examiner (Fig 3).


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)

Representative color Doppler image for measurement of renal flow velocities.Typical recordings of intrarenal flow velocities measurement in segmental renal arteries were performed with color Doppler ultrasound in lean and leptin-deficient (ob/ob) mice at 21 weeks of age. The pulsatility flow profile was used for measurement of peak systolic velocity (PSV) (red line), mean velocity (MV) (blue line) and lowest diastolic velocity (LDV) (yellow line) for calculation of pulsatility index and resistive index. A: Renal flow velocity profile in lean mice. B: Renal flow velocity profile in ob/ob mice.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130648.g002: Representative color Doppler image for measurement of renal flow velocities.Typical recordings of intrarenal flow velocities measurement in segmental renal arteries were performed with color Doppler ultrasound in lean and leptin-deficient (ob/ob) mice at 21 weeks of age. The pulsatility flow profile was used for measurement of peak systolic velocity (PSV) (red line), mean velocity (MV) (blue line) and lowest diastolic velocity (LDV) (yellow line) for calculation of pulsatility index and resistive index. A: Renal flow velocity profile in lean mice. B: Renal flow velocity profile in ob/ob mice.
Mentions: Ultrasound examination of the right kidney was performed at 21 weeks of age in combination with the cardiac echocardiography investigation. Standard B-mode examination of the kidney was performed in a long-axis view using the same ultrasound imaging system as described above. Following color-Doppler mapping of the renal vascular tree using a color-Doppler frequency of 32 MHz, a cursor was placed at the central segmental artery and renal flow velocity was measured using pulse wave Doppler (Fig 2). Kidney length was measured off-line at standard B-mode long axis view, blinded to the examiner (Fig 3).

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