Genetic Factors Limit Growth of Pathogenic Muscle Cells

Genetic factors have been identified that can turn stem cells into the type of muscle cells that reside in the wall of blood vessels.

The switch to these muscle cells might be used in the future to limit growth of vascular muscle cells that cause narrowing of arteries leading to heart attacks and strokes; limit formation of blood vessels that feed cancers; or make new blood vessels for organs that are not receiving sufficient blood flow.

Micro (mi)R-145 RNA and miR-143, work together to stop the pathologic division of vascular smooth muscle cells (VSMCs). These small RNAs affect the amount of protein synthesized by the cell from their target messenger (mRNAs-the blueprints for translating the genetic code into proteins. miR-145 and miR-143 together control the synthesis of a network of "master regulators" that control VSMCs, and thereby were able to function as a central "switch" for the behavior of these important cells.

The Deepak Srivastava laboratory at the Mission Bay campus of the Gladstone Institute of Cardiovascular Disease (GICD; San Francisco, CA, USA) focuses on transcriptional and translational regulation of key pathways in cardiac progenitor cell differentiation and cardiac morphogenesis.

The scientists at GICD discovered the genetic causes of different forms of familial congenital heart disease and elucidated the disease mechanisms. They found that several of the regulatory microRNAs (miRNAs) have critical roles in cardiac development and postnatal heart function. They use pathways regulating early cardiac commitment as a method toward the therapeutic application of embryonic stem (ES) cells for treatment of heart disease.

"The ability of miR-145 to efficiently direct the cell fate of vascular smooth muscle cells from stem cells represents the power of these tiny microRNAs to exert major effects on cells," said Deepak Srivastava, M.D., GICD director, and senior author of the study published online on July 5, 2009, in advance of print publication in the journal Nature.

Related Links:
Gladstone Institute of Cardiovascular Disease