Why the study?
1, 25-dihydroxy Vitamin D3 attenuates LVH, but the underlying mechanisms remain to be portrayed in-depth.
Does 1, 25-dihydroxy Vitamin D3 reduce pressure overload-induced cardiac hypertrophy and Rac1 expression in Wistar rats?
Does 1, 25-dihydroxy Vitamin D3 reduce pressure overload-induced cardiac hypertrophy and Rac1 expression in Wistar rats?
Vitamin D mitigates pressure overload-induced left ventricular hypertrophy in rats, potentially by suppressing small GTPase Rac1 expression and reducing oxidative stress.
Answers are grounded in this paper and cite their sources.
May support Rac1-targeted VitD effects in rodent hypertrophy models; leaves open human translation.
BACKGROUND: 1, 25-dihydroxy Vitamin D3 (VitD) attenuates left ventricular hypertrophy (LVH), but the mechanisms remain to be portrayed in-depth. The small GTPase Rac1 plays a pivotal role in cardiovascular pathology, especially LVH. Here, we tested whether VitD exerts its anti-LVH effects by counteracting the small GTPase Rac1 expression. METHODS: In Wistar rats, pressure overload-induced LVH was created by abdominal aortic banding. The animals were intraperitoneally administered VitD (0.1 µg/kg/d). Blood pressure was measured via carotid artery cannulation. Real-time RT-PCR and Western blotting were performed to assess the mRNA and protein expression, respectively. Myocardium was stained for determination of cardiomyocytes area and fibrosis. Lipid peroxidation levels and the activities of antioxidant enzymes were measured in left ventricular tissue. RESULTS: VitD significantly reduced hypertrophy markers (blood pressure, heart-to-body weight ratio, cardiomyocytes area, fibrosis as well as atrial and brain natriuretic peptides mRNA levels) compared to untreated groups (P < 0.05). VitD also improved the activity of antioxidant enzymes and reduced lipid peroxidation levels in the myocardium (P < 0.05). LVH hearts of untreated animals displayed a significant increase in Rac1 expression compared with the control group (P < 0.05). In contrast, cardiac Rac1, at either mRNAs or protein levels, was markedly lower in LVH animals receiving VitD compared with their untreated counterparts (P < 0.05). CONCLUSION: Our findings attest that VitD mitigates hallmarks of LVH imparted by pressure overload. Notably, VitD appears to perform its anti-LVH function partly through small GTPase Rac1 suppression. This, in turn, provides a robust incentive to consider VitD before LVH culminates in HF devastating disease.
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Moradi et al. (2021) studied this question.
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