Study finds DMD affects vascular muscles as well as skeletal ones
Findings highlight need for therapies targeting blood vessel abnormalities
Duchenne muscular dystrophy (DMD) causes dysfunction of muscle cells that help move blood through the circulatory system, a study found.
The changes associated with DMD included dysregulated activity of some genes and altered dynamics and structure of mitochondria, the cell’s powerhouses.
“These findings highlight the importance of targeting vascular [blood vessel] abnormalities in therapeutic strategies to slow disease progression,” the researchers wrote.
The study, “Impact of dystrophin deficiency on vascular smooth muscle cell,” was published in Scientific Reports.Â
DMD is caused by mutations in the gene that encodes dystrophin, a protein essential for preserving muscle health. Muscles lacking dystrophin accumulate damage over time, leading to the progressive muscle weakness and wasting that characterizes the disease.
Beyond skeletal and cardiac muscles
Studies on how muscle is affected by DMD have focused mainly on skeletal muscles (the muscles needed for movement) and cardiac muscles in the heart. But these aren’t the only types of muscle cells in the body. While the heart does the lion’s share of work to pump blood through the circulatory system, it doesn’t work alone: Blood vessels are lined with muscle cells, called vascular smooth muscle cells (VSMCs), which are crucial for squeezing blood out to parts of the body that are far from the heart.
A team of U.S. scientists set out to investigate if and how VSMCs may be affected by DMD. The scientists used multiple lab models for their experiments, including a mouse model of DMD and a cell model using VSMCs grown using cells collected from people with or without DMD.
The researchers found that VSMCs derived from DMD patients had problems fully maturing, and they expressed abnormally low levels of proteins that are needed for muscle contraction. VSMCs from DMD patients also showed dysregulation of mitochondria, cellular structures key to energy generation. In particular, the balance between mitochondrial fission and fusion (division), which is fundamental for maintaining cellular function, was altered in DMD cells as mitochondrial fission was enhanced.
And when the cells were exposed to oxidative stress (a type of cell damage caused by oxygen-containing molecules), these VSMCs showed more signs of programmed cell death than healthy VSMCs.
Analyses of DMD mice showed changes in the cellular architecture of VSMCs surrounding the aorta (the main vessel that takes oxygen-rich blood from the heart to the rest of the body), with regions of thin or thickened vessels.
The data suggest that DMD causes problems with muscle cells throughout the circulatory system, highlighting the need to consider VSMCs when developing treatments aiming to improve muscle cell health in DMD, the scientists said.
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