Short-Term Pharmacological Induction of Arterial Stiffness and Hypertension with Angiotensin II Does Not Affect Learning and Memory and Cerebral Amyloid Load in Two Murine Models of Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. AngII Treatment Affects hAPP23+/− and hAPPswe/PSEN1dE9 Mice Differently
2.2. AngII Treatment Induces Hypertrophic Cardiomyopathy
2.3. AngII Treatment Induces Hypertension
2.4. AngII Treatment Induces In Vivo Arterial Stiffness
2.5. AngII Treatment Does Not Lead to Impaired MWM Acquisition Trial Performance
2.6. AngII Treatment Does Not Result in Impaired Probe Trial Performances
2.7. AngII Treatment of AD Mice Does Not Result in Increased Amyloid Load
3. Discussion
4. Materials and Methods
4.1. Experimental Animals and Osmotic Minipump Implantation
4.2. Visuospatial Learning and Memory
4.3. Blood Pressure Measurements
4.4. Echocardiography
4.5. Non-Invasive Pulse Wave Velocity (PWV) Measurements of the Aortic Abdominal Aorta (aPWV)
4.6. Rodent Oscillatory Tension Set-Up for Arterial Compliance (ROTSAC)
4.7. Histology
4.8. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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C57BL/6 | hAPP23+/− | ||||||
---|---|---|---|---|---|---|---|
PBS (n = 14) | AngII (n = 12) | PBS (n = 11) | AngII (n = 11) | ptreatment | pgenotype | ptreatment × genotype | |
Body weight (g) | 27 ± 1 | 27 ± 1 | 27 ± 1 | 24 ± 1 $ | ns | ** | ns |
Survival, genotype (%) | 74 | - | 80 | - | - | ns | - |
Survival, treatment (%) | 100 | 57 | 76 | 80 | - | ns | - |
AAA incidence (%) | - | 25 | - | 31 | ns | - | - |
C57BL/6 | hAPPswe/ PSEN1dE9 | ||||||
PBS (n = 14) | AngII (n = 13) | PBS (n = 12) | AngII (n = 11) | ptreatment | pgenotype | ptreatment × genotype | |
Body weight (g) | 34 ± 1 | 32 ± 1 £ | 33 ± 1 | 32 ± 1 | ** | ns | ns |
Survival, genotype (%) | 90 | - | 75 | - | - | ns | - |
Survival, treatment (%) | 100 | 58 | 95 | 72 | - | 0.09 | - |
AAA incidence (%) | - | 69 | - | 31 | *** | - | - |
C57BL/6 | hAPP23+/− | ||||||
---|---|---|---|---|---|---|---|
PBS (n = 14) | AngII (n = 12) | PBS (n = 11) | AngII (n = 11) | ptreatment | pgenotype | ptreatment × genotype | |
Heart weight (mg) | 165 ± 5 | 188 ± 5 £ | 141 ± 3 | 183 ± 8 $$$ | *** | * | ns |
Heart weight (%) | 0.53 ± 0.01 | 0.58 ± 0.01 | 0.51 ± 0.01 | 0.69 ± 0.04 $$$ | *** | * | ** |
IVS,d (mm) | 1.2 ± 0.1 | 1.1 ± 0.1 | 1.1 ± 0.1 | 1.3 ± 0.1 | ns | ns | ns |
LVID,d (mm) | 3.7 ± 0.1 | 3.7 ± 0.1 | 3.6 ± 0.1 | 3.4 ± 0.2 | ns | 0.06 | ns |
LVPW,d (mm) | 1.1 ± 0.1 | 1.1 ± 0.1 | 1.1 ± 0.1 | 1.4 ± 0.1 | 0.08 | 0.07 | ns |
LV mass (mg) | 172 ± 11 | 167 ± 10 | 157 ± 11 | 187 ± 18 | ns | ns | ns |
LV mass/BW (10−3) | 5.5 ± 0.3 | 5.2 ± 0.3 | 5.7 ± 0.5 | 7.1 ± 0.7 | ns | * | ns |
LV volume,d (µL) | 60 ± 4 | 61 ± 5 | 54 ± 4 | 49 ± 6 | ns | 0.08 | ns |
Stroke volume (µL) | 42 ± 3 | 42 ± 3 | 39 ± 2 | 33 ± 3 | ns | 0.08 | ns |
EF (%) | 71 ± 2 | 70 ± 3 | 73 ± 2 | 71 ± 3 | ns | ns | ns |
FS (%) | 40 ± 2 | 39 ± 2 | 42 ± 2 | 40 ± 2 | ns | ns | ns |
E/A (none) | 1.4 ± 0.1 | 1.4 ± 0.1 | 1.5 ± 0.3 | 1.6 ± 0.1 | ns | ns | ns |
E/E’ (none) | 32 ± 3 | 29 ± 4 | 35 ± 4 | 51 ± 7 | ns | * | ns |
IVRT (ms) | 19 ± 1 | 21 ± 1 | 23 ± 2 | 24 ± 3 | ns | 0.07 | ns |
Deceleration (ms) | 17 ± 1 | 15 ± 1 | 16 ± 2 | 21 ± 2 | ns | ns | ns |
C57BL/6 | hAPPswe/ PSEN1dE9 | ||||||
---|---|---|---|---|---|---|---|
PBS (n = 14) | AngII (n = 13) | PBS (n = 12) | AngII (n = 11) | ptreatment | pgenotype | ptreatment × genotype | |
Heart weight (mg) | 182 ± 5 | 218 ± 7 £££ | 158 ± 3 | 204 ± 9 $$$ | *** | ** | ns |
Heart weight (%) | 0.53 ± 0.01 | 0.68 ± 0.02 £££ | 0.48 ± 0.01 | 0.65 ± 0.02 $$$ | *** | * | ns |
IVS,d (mm) | 1.2 ± 0.1 | 1.4 ± 0.1 | 1.1 ± 0.1 | 1.3 ± 0.1 | * | ns | ns |
LVID,d (mm) | 3.6 ± 0.1 | 3.8 ± 0.1 | 3.6 ± 0.1 | 3.6 ± 0.2 | ns | ns | ns |
LVPW,d (mm) | 1.0 ± 0.1 | 1.2 ± 0.1 | 1.0 ± 0.1 | 1.1 ± 0.1 | * | ns | ns |
LV mass (mg) | 170 ± 21 | 224 ± 17 | 148 ± 15 | 186 ± 18 | * | ns | ns |
LV mass/BW (10−3) | 4.9 ± 0.6 | 7.0 ± 0.5 £ | 4.5 ± 0.5 | 5.9 ± 0.5 | ** | ns | ns |
LV volume,d (µL) | 57 ± 4 | 63 ± 4 | 55 ± 4 | 54 ± 6 | ns | ns | ns |
Stroke volume (µL) | 42 ± 3 | 42 ± 2 | 38 ± 3 | 39 ± 3 | ns | ns | ns |
EF (%) | 73 ± 2 | 68 ± 3 | 70 ± 2 | 74 ± 4 | ns | ns | ns |
FS (%) | 42 ± 2 | 38 ± 3 | 39 ± 2 | 43 ± 4 | ns | ns | ns |
E/A (none) | 1.6 ± 0.2 | 1.7 ± 0.1 | 1.4 ± 0.3 | 1.5 ± 0.1 | ns | ns | ns |
E/E’ (none) | 32 ± 5 | 23 ± 4 | 31 ± 5 | 22 ± 4 | ns | ns | ns |
IVRT (ms) | 21 ± 2 | 22 ± 1 | 22 ± 1 | 24 ± 3 | ns | ns | ns |
Deceleration (ms) | 16 ± 1 | 18 ± 2 | 17 ± 1 | 17 ± 1 | ns | ns | ns |
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Hendrickx, J.O.; Calus, E.; De Deyn, P.P.; Van Dam, D.; De Meyer, G.R.Y. Short-Term Pharmacological Induction of Arterial Stiffness and Hypertension with Angiotensin II Does Not Affect Learning and Memory and Cerebral Amyloid Load in Two Murine Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 2738. https://doi.org/10.3390/ijms23052738
Hendrickx JO, Calus E, De Deyn PP, Van Dam D, De Meyer GRY. Short-Term Pharmacological Induction of Arterial Stiffness and Hypertension with Angiotensin II Does Not Affect Learning and Memory and Cerebral Amyloid Load in Two Murine Models of Alzheimer’s Disease. International Journal of Molecular Sciences. 2022; 23(5):2738. https://doi.org/10.3390/ijms23052738
Chicago/Turabian StyleHendrickx, Jhana O., Elke Calus, Peter Paul De Deyn, Debby Van Dam, and Guido R. Y. De Meyer. 2022. "Short-Term Pharmacological Induction of Arterial Stiffness and Hypertension with Angiotensin II Does Not Affect Learning and Memory and Cerebral Amyloid Load in Two Murine Models of Alzheimer’s Disease" International Journal of Molecular Sciences 23, no. 5: 2738. https://doi.org/10.3390/ijms23052738