Cardioprotective effect of Vitamin D on cardiac hypertrophy through improvement of mitophagy and apoptosis in an experimental rat model of levothyroxine -induced hyperthyroidism.

BACKGROUND: Mitochondria are known to be involved in mediating the calorigenic effects of thyroid hormones. With an abundance of these hormones, alterations in energy metabolism and cellular respiration take place, leading to the development of cardiac hypertrophy. Vitamin D has recently gained attention due to its involvement in the regulation of mitochondrial function, demonstrating promising potential in preserving the integrity and functionality of the mitochondrial network. The present study aimed to investigate the therapeutic potential of Vitamin D on cardiac hypertrophy induced by hyperthyroidism, with a focus on the contributions of mitophagy and apoptosis as possible underlying molecular mechanisms. METHODS AND RESULTS: The rats were divided into three groups: control; hyperthyroid; hyperthyroid + Vitamin D. Hyperthyroidism was induced by Levothyroxine administration for four weeks. Serum thyroid hormones levels, myocardial damage markers, cardiac hypertrophy indices, and histological examination were assessed. The assessment of Malondialdehyde (MDA) levels and the expression of the related genes were conducted using heart tissue samples. Vitamin D pretreatment exhibited a significant improvement in the hyperthyroidism-induced decline in markers indicative of myocardial damage, oxidative stress, and indices of cardiac hypertrophy. Vitamin D pretreatment also improved the downregulation observed in myocardial expression levels of genes involved in the regulation of mitophagy and apoptosis, including PTEN putative kinase 1 (PINK1), Mitofusin-2 (MFN2), Dynamin-related Protein 1 (DRP1), and B cell lymphoma-2 (Bcl-2), induced by hyperthyroidism. CONCLUSIONS: These results suggest that supplementation with Vitamin D could be advantageous in preventing the progression of cardiac hypertrophy and myocardial damage.

Two New Variants in FYCO1 Are Responsible for Autosomal Recessive Congenital Cataract in Iranian Population.

The purpose of this experimental study was to investigate the genetic etiology of congenital cataract (CC) manifesting an autosomal recessive pattern of inheritance in four Iranian families. Affected individuals and their normal first-degree relatives in each family were included in the present study. The genomic DNA of the blood samples was extracted from all participants, and one affected member belonging to each family was subjected to Whole Exome Sequencing (WES). Using bidirectional Sanger sequencing, the identified variants were validated by co-segregation analysis. Two different mutations were detected in the FYCO1 gene encoding FYVE and coiled-coil domain-containing protein. A previously reported missense mutation, c.265C>T (p.Arg89Cys), was found in one Iranian family for the first time, and a combination of two variants in a single codon, c.[265C>T;267C>A] (p.Arg89X), was identified in the three other families. On the other hand, accompanying the c.265C>T mutation, the presence of the c.267C>A polymorphism leads to a premature stop codon. In-Silico Analysis of FYCO1 protein demonstrated that RUN domain will be interrupted so that the large part of functional protein will be eliminated due to this novel variant. FYCO1 has been proved to be involved in human lens development and transparency. Its mutations, therefore, result in CC. Herein, we reported the first autosomal recessive CC patients with c.265C>T (p.Arg89Cys) or c.[265C>T;267C>A] variant in Iranian population for the FYCO1 gene. FYCO1 mutations could be tracked for preventive objectives or even be targeted as therapeutic candidates via treatment approaches in the future.