Cardiovascular disease (CV) remains the leading cause of death worldwide. Low levels of vitamin D are associated with high risk of myocardial infarction, even after controlling for factors associated with coronary artery disease. A growing body of evidence suggests that vitamin D plays an important role in CV related signaling pathways. However, little is known about the molecular mechanism by which vitamin D modulates cardiac development. The Wnt signaling pathway plays a pivotal role in tissue development by controlling stem cell renewal, lineage selection and even more importantly heart development. In this study, we examined the role of 1,25-D3 (active form of vitamin D) on cardiomyocyte proliferation, apoptosis, cell phenotype, cell cycle progression and differentiation into cardiomyotubes. We determined that the addition of 1,25-D3 to cardiomyocytes cells: 1) Inhibits cell proliferation without promoting apoptosis; 2) Decreases expression of genes related to the regulation of the cell cycle; 3) Promotes cardiomyotubes formation; 4) Induces the expression of Casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and 5) Increases the expression of the noncanonical Wnt11, which it has been demonstrated to induce cardiac differentiation during embryonic development in adult cells. In conclusion, we postulate that vitamin D promotes cardiac differentiation through a negative modulation of the canonical Wnt signaling pathway and by up-regulating the expression of Wnt11. These results suggest that vitamin D repletion to prevent and/or improve cardiovascular disorders that are linked to abnormal cardiac differentiation, such as post infarction cardiac remodeling, deserve further study.

Cardiovascular disease (CV) remains the leading cause of death worldwide. Low levels of vitamin D are associated with high risk of myocardial infarction, even after controlling for factors associated with coronary artery disease. A growing body of evidence suggests that vitamin D plays an important role in CV related signaling pathways. However, little is known about the molecular mechanism by which vitamin D modulates cardiac development. The Wnt signaling pathway plays a pivotal role in tissue development by controlling stem cell renewal, lineage selection and even more importantly heart development. In this study, we examined the role of 1,25-D 3 (active form of vitamin D) on cardiomyocyte proliferation, apoptosis, cell phenotype, cell cycle progression and differentiation into cardiomyotubes. We determined that the addition of 1,25-D 3 to cardiomyocytes cells: 1) Inhibits cell proliferation without promoting apoptosis; 2) Decreases expression of genes related to the regulation of the cell cycle; 3) Promotes cardiomyotubes formation; 4) Induces the expression of Casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and 5) Increases the expression of the noncanonical Wnt11, which it has been demonstrated to induce cardiac differentiation during embryonic development in adult cells. In conclusion, we postulate that vitamin D promotes cardiac differentiation through a negative modulation of the canonical Wnt signaling pathway and by upregulating the expression of Wnt11. These results suggest that vitamin D repletion to prevent and/or improve cardiovascular disorders that are linked to abnormal cardiac differentiation, such as post infarction cardiac remodeling, deserve further study.