Differential Left and Right Carotid Artery Blood Flow and Altered Hippocampal Mitochondrial Function After Transverse Aortic Constriction in Aging Rats

Figures

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  Figure 1. TAC carotid hemodynamic phenotype is characterized by greater right and lower left carotid blood flow that does not worsen with time. A, Doppler ultrasound waveforms of the left and right carotid arteries of TAC animals. B, Peak carotid blood flow velocity in the right and left carotids of TAC and SHAM animals 20, 30, and 40 weeks postsurgery. C, Calculated right and left carotid flow rate in TAC and SHAM animals 20, 30, and 40 weeks postsurgery. D, Blood flow pulsatility in the right and left carotid of TAC and SHAM animals 20, 30, and 40 weeks postsurgery. *P<0.05, **P<0.01, ***P<0.001. Data are presented as mean+SEM. SHAM indicates sham‐operated controls; and TAC, transverse aortic constriction.

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  Figure 2. Hippocampal mitochondrial respiration is impaired in the right hemisphere in TAC animals, and SHAM animals display sex dimorphisms not present in TAC. A, Hippocampal mitochondrial respiration in right and left hemisphere of TAC and SHAM animals 40 weeks postsurgery. B, Right and left hemispheric hippocampal. Mitochondrial respiration in male and female TAC animals 40 weeks postsurgery. C, Right and left hemispheric hippocampal. Mitochondrial respiration in male and female SHAM animals 40 weeks postsurgery. *P<0.05, ***P<0.001. Data are presented as mean+SEM. CI indicates complex I; CII, complex II; ETS, electron transfer system; F, female; FCCP, carbonyl cyanide p‐trifluoromethoxyphenylhydrazone; G, glutamte; JO, oxygen consumption; LEAK, leak respiration; M, malate; M, male; P, pyruvate; ROX, residual nonmitochondrial oxygen consumption; SHAM, sham‐operated controls; and TAC, transverse aortic constriction.

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  Figure 3. High carotid blood flow velocity and pulsatility are negatively associated with hippocampal mitochondrial respiratory states. A, Scatterplot depicting the negative association between carotid artery velocity and pulsatility to CI&II coupled hippocampal respiration 40 weeks postsurgery. B, Scatterplot depicting the negative association between carotid artery velocity and pulsatility to CII uncoupled hippocampal respiration 40 weeks postsurgery. CI indicates complex I; CII, complex II; ETS, electron transfer system; and JO, oxygen consumption.

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  Figure 4. Hippocampal protein expression of mitochondrial fusion markers is greater in TAC animals and among females in TAC and SHAM. A, Protein expression of mitochondrial fusion markers in the right and left hippocampus of TAC and SHAM animals 40 weeks postsurgery. B, Protein expression of mitochondrial fusion markers in male and female TAC animals 40 weeks postsurgery. C, Protein expression of mitochondrial fusion markers in male and female SHAM animals 40 weeks postsurgery. *P<0.05, **P<0.01. Data are presented as mean+SEM. A.U indicates arbitrary units; F, female; HSP‐60, heat shock protein‐60; L, left; L‐OPA1, OPA1 long isoform; M, male; MFN, mitofusin 2; OPA1, optic atrophy 1; R, right; SHAM, sham‐operated controls; S‐OPA1, OPA1 short isoform; and TAC, transverse aortic constriction.

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  Figure 5. Hippocampal protein expression of mitochondrial fission markers are not altered in TAC, but sex differences are present in SHAM controls. A, Protein expression of mitochondrial fission markers in TAC and SHAM. B, Protein expression of mitochondrial fission markers in male and female TAC animals 40 weeks postsurgery. C, Protein expression of mitochondrial fission markers in male and female SHAM animals 40 weeks postsurgery. *P<0.05. Data are presented as mean+SEM. A.U indicates arbitrary units; DRP1, dynamin‐related protein 1; F, female; FIS1, fission 1; L, left; M, male; R, right; SHAM, sham‐operated controls; and TAC, transverse aortic constriction.

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  Figure 6. Protein expression of glucose transporters is not altered in TAC 40 weeks postsurgery. Data are presented as mean+SEM. A.U. indicates arbitrary units; GLUT‐1, glucose transporter 1; GLUT‐3, glucose transporter 3; L, left; R, right; SHAM, sham‐operated controls; and TAC, transverse aortic constriction.