They found that when SRF and myocardin work together, they turn on a protein known as SREBP2, which inhibits a molecule known as LRP-1, which helps the body remove amyloid beta.
When compared to the smooth muscle cells from healthy adults, it was found that the cells from patients with Alzheimer's disease had about five times as much myocardin and four times as much SRF, about five times as much SREBP2, and about 60 percent less LRP-1.
On the other hand, by boosting the levels of SRF and myocardin in the healthy cells, the changes lowered by about 65 percent those cells' ability to remove amyloid beta.
Modulation of pulmonary vascular smooth muscle cell phenotype in hypoxia: role of cGMP-dependent protein kinase and myocardin
. Am J Physiol Lung Cell Mol Physiol 2009; 296: L780-L789, doi: 10.1152/ajplung.90295.2008.
Van De Watering et al., "Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardin
," Cardiovascular Research, vol.
On the other hand, class II HDACs prevent cardiac hypertrophy by blocking the activity of several prohypertrophic transcription factors, including SRF, GATA4, nuclear factor of activated T-cells (NFAT), and myocardin .
Zhang et al., "Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin," Molecular and Cellular Biology, vol.
Tang et al., "Acetylation of myocardin is required for the activation of cardiac and smooth muscle genes," The Journal of Biological Chemistry, vol.
Olson, "The myocardin
family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis," Genes and Development, vol.
However, preincubation of MSCs with BIX01294 allowed for the induced expression of the cardiac transcription factors Nkx2.5, GATA4, and myocardin in response to Wnt11 (Figures 3(a), 3(b), and 3(c)).
Additionally, we have shown that the TSA acted synergistically with BIX01294 to upregulate GATA4, Nkx2.5, and myocardin in response to Wnt11.
Deane et al., "Serum response factor and myocardin
mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype," Proceedings of the National Academy of Sciences of the United States of America, vol.