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. 2025 Feb;45(2):341-343.
doi: 10.1161/ATVBAHA.124.321848. Epub 2024 Dec 12.

Myocardial Hyperemia via Cardiomyocyte Catabolism of β-Hydroxybutyrate

Kara R Gouwens #  1   2 , Yibing Nong #  1 , Ning Chen  1 , Emily B Schulman-Geltzer  1 , Helen E Collins  1 , Bradford G Hill  1 , Matthew A Nystoriak  1   3
Affiliations

Myocardial Hyperemia via Cardiomyocyte Catabolism of β-Hydroxybutyrate

Kara R Gouwens et al. Arterioscler Thromb Vasc Biol. 2025 Feb.

Erratum in

No abstract available

Keywords: liver; mammals; microcirculation; oxygen; perfusion.

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Conflict of interest statement

None.

Figures

Figure 1.
Figure 1.. Cardiomyocyte ketone body catabolism underlies 3-OHB-induced myocardial hyperemia.
A. (i) Plasma [3-OHB] in male (closed; n=3) and female (open; n=4) C57BL/6J mice at baseline and 5–15 min 3-OHB infusion; 3-OHB vs. baseline: p<0.001; male vs. female: p=0.22, Mixed-effects. (ii) Representative long-axis B-mode and nonlinear contrast (NLC) mode images (background: before contrast infusion). (iii) Exemplary intensity replenishment plots, for myocardial blood flow calculation (as described in ), with exponential fits (y=A(1–e-βt)); rBV (A/cavity): relative blood volume, β (sec−1): blood exchange frequency. (iv) Relationship between plasma 3-OHB and myocardial perfusion measured at baseline (black) and during 3-OHB infusion (blue); data are fit with linear regression and 95% confidence intervals, p=0.008, Pearson correlation coefficient, n=7 (3 male, closed; 4 female, open). Inset shows summarized perfusion at baseline and 3-OHB infusion; p value from paired t-test; n=8 (4 male, 4 female). B. (i) Qualitative images showing isolation and cannulation of murine small diameter left anterior coronary arteries; images are representative of arteries with maximum passive diameter of 193 ± 15 μm (n=14 arteries) at 80 mmHg intravascular pressure. (ii–iii) Diameter recordings from coronary arteries isolated from male C57BL/6J mice with intravascular pressure-induced (80 mmHg, n=5; ii) and agonist-induced tone (100 nM U46619, n=9; iii) before and after treatment with 3-OHB (0.1–5 mM). Data are expressed as percent change in diameter relative to maximum passive diameters recorded in Ca2+-free buffer (–Ca2+); p values are from Friedman test. C. (i) Scheme showing canonical ketone body oxidation pathway. (ii) Representative Western blots showing immunoreactive bands for BDH1, BDH2, and SCOT1 in whole heart lysates from control (Cre–) and csBDH1−/− (Cre+) male mice. Total protein (stain-free gel) is shown as a loading control. (iii) Relative immunoreactive band densities from control and csBDH1−/− mice; p values from unpaired t-tests; n=6 each. D. (i) Plasma 3-OHB following 10 min of 3-OHB infusion in control (n=6) and csBDH−/− (n=5) male mice. 3-OHB (+) vs. baseline (–): Mixed-effects with uncorrected Fischer’s Least Significant Difference test. (ii) Summarized perfusion at baseline (–) and during 3-OHB infusion (+) in control (n=6) and csBDH−/− (n=7) mice; p values from paired t-tests. (iii) Myocardial perfusion relative to cardiac work (HR × SW) at baseline and during 3-OHB infusion in control (n=6) and csBDH1−/− (n=6) mice; p values from Wilcoxon matched-pairs signed rank test.
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References

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