Key result
Treatment with the activated vitamin D analog paricalcitol significantly attenuated TAC-induced cardiac hypertrophy, reducing the HW/BW ratio increase by 18% compared to vehicle in 1a-OHase-/- mice.
Why the study?
Altered vitamin D signaling is associated with cardiac dysfunction, but the pathogenic mechanism is not clearly understood.
Vitamin D deficiency exacerbates pressure overload-induced cardiac dysfunction and calcium handling abnormalities, which can be rescued by vitamin D supplementation in a mouse model.
Answers are grounded in this paper and cite their sources.
No immediate clinical implications for vitamin D analogs in HF; leaves open translation of paricalcitol effects to patients.
AIM: Altered vitamin D signaling is associated with cardiac dysfunction, but the pathogenic mechanism is not clearly understood. We examine the mechanism and the role of vitamin D signaling in the development of cardiac dysfunction. METHODS AND RESULTS: We analyzed 1α-hydroxylase (1α-OHase) knockout (1α-OHase-/-) mice, which lack 1α-OH enzymes that convert the inactive form to hormonally active form of vitamin D. 1α-OHase-/- mice showed modest cardiac hypertrophy at baseline. Induction of pressure overload by transverse aortic constriction (TAC) demonstrated exaggerated cardiac dysfunction in 1α-OHase-/- mice compared to their WT littermates with a significant increase in fibrosis and expression of inflammatory cytokines. Analysis of calcium (Ca2+) transient demonstrated profound Ca2+ handling abnormalities in 1α-OHase-/- mouse cardiomyocytes (CMs), and treatment with paricalcitol (PC), an activated vitamin D3 analog, significantly attenuated defective Ca2+ handling in 1α-OHase-/- CMs. We further delineated the effect of vitamin D deficiency condition to TAC by first correcting the vitamin D deficiency in 1α-OHase-/- mice, followed then by either a daily maintenance dose of vitamin D or vehicle (to achieve vitamin D deficiency) at the time of sham or TAC. In mice treated with vitamin D, there was a significant attenuation of TAC-induced cardiac hypertrophy, interstitial fibrosis, inflammatory markers, Ca2+ handling abnormalities and cardiac function compared to the vehicle treated animals. CONCLUSIONS: Our results provide insight into the mechanism of cardiac dysfunction, which is associated with severely defective Ca2+ handling and defective vitamin D signaling in 1α-OHase-/- mice.
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Choudhury et al. (2014) studied Cardiac dysfunction and Vitamin D deficiency. Paricalcitol vs. Vehicle was evaluated on Cardiac hypertrophy (HW/BW ratio) (p=<0.05). Treatment with the activated vitamin D analog paricalcitol significantly attenuated TAC-induced cardiac hypertrophy, reducing the HW/BW ratio increase by 18% compared to vehicle in 1a-OHase-/- mice.
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