What causes multisystemic smooth muscle dysfunction?

What causes multisystemic smooth muscle dysfunction?

Multisystemic smooth muscle dysfunction syndrome (MSMDS) is a rare vascular disorder caused by a mutation in the actin alpha 2 gene (ACTA2) which encodes for a protein called alpha smooth muscle actin isotype 2. The disorder is most often caused by a heterozygous de novo mutation at p. Arg179His.

What does alpha smooth muscle actin do?

Abstract. Alpha-smooth muscle actin (SMA), an actin isoform that contributes to cell-generated mechanical tension, is normally restricted to cells of vascular smooth muscle, but SMA can also be expressed in certain non-muscle cells, most notably myofibroblasts.

Where is alpha smooth muscle actin found?

alpha-Smooth muscle (alpha-sm) actin, an isoform typical of smooth muscle cells (SMC) and present in high amounts in vascular SMC, was demonstrated in the cytoplasm of pericytes of various rat and human organs by means of immunocytochemistry at the electron microscopic level.

What is ACTA2 mutation?

ACTA2 gene mutations that are associated with familial TAAD change single protein building blocks (amino acids) in the smooth muscle α-2 actin protein. These changes likely affect the way the protein functions in smooth muscle contraction, interfering with the sarcomeres’ ability to prevent arteries from stretching.

What happens if your smooth muscles stopped working?

Muscle function loss occurs when your muscles don’t work or move normally. Complete muscle function loss, or paralysis, involves being unable to contract your muscles normally. If your muscles lose function, you won’t be able to properly operate the affected parts of your body.

What do myofibroblasts do?

Myofibroblasts are the mesenchymal cell type responsible for wound healing and tissue repair across all organs and various physiological states, including cancer [31].

What cells express alpha smooth muscle actin?

Myofibroblasts. Myofibroblasts express α-smooth muscle actin (α-SMA) and have contractile and secretory properties that are central to controlling tissue architecture [6]. They express a panel of markers that have been correlated with the site of origin.

What is alpha SMA a marker of?

α-Smooth muscle actin (α-SMA) is used as a marker for a subset of activated fibrogenic cells, myofibroblasts, which are regarded as important effector cells of tissue fibrogenesis.

What does ACTA2 stand for?

ACTA2 (actin, α-2, smooth muscle, aorta; OMIM *102620) is the most frequently mutated gene causing familial thoracic aortic aneurysms and dissection and is responsible for 12% to 21% of familial thoracic aortic aneurysms and dissection cases.

What is the COL3A1 gene?

The COL3A1 gene provides instructions for making type III collagen. Collagens are a family of proteins that strengthen and support many tissues in the body. Type III collagen is found in the skin, lungs, intestinal walls, and the walls of blood vessels.