Inosine Triphosphate Pyrophosphatase as a Candidate Associated with White Matter Abnormalities in Chronic Heart Failure

In symptomatic Stage C chronic heart failure, global white matter hyperintensity volume increased more than in Stage B (4,717{+/-}5,335 vs. 2,116{+/-}3,134 mm3; P=0.027), mainly near anterior periventricular white matter.

• Why it matters: White matter hyperintensities are common in aging and also in chronic heart failure, but the biological factors linking CHF severity to white matter injury are unclear.
• What they did: In a longitudinal prospective cohort (32 Stage B, 23 Stage C), plasma proteomics plus two-step Mendelian randomization identified inosine triphosphate pyrophosphatase (ITPA) as the only candidate linked to both Stage C CHF and WMH progression (P<0.05), with rare ITPA variants associated with FA.
• The result: In CHF rats, anterior pericallosal cortex showed reduced myelin basic protein density and FA with increased ITPA expression versus sham, and recombinant ITPA exposure reduced total axonal length in cultured cortical neurons.

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