Calcium-Signaling Pathway Regulates Inflammatory Gene Expression following Heart Attack
Study in Journal of Clinical Investigation found CFB to be the expressed the most.!--h2>
Investigators at the University of Iowa found a link between inflammation in the heart muscle following a heart attack and a previously known enzyme called calcium/calmodulin-dependent protein kinase II (CaM kinase II). The research showed that a heart attack triggers increased expression of a set of proinflammatory genes, and inhibition of CaM kinase II substantially reduced this effect.
They also found that a cluster of these genes were differently expressed depending on whether CAM kinase II was active or inhibited. Of these genes, complement factor B (CFB), which has been implicated in other inflammatory diseases, was most highly regulated.
Further studies on CaMKII done in culture revealed that it is synthesized in heart muscle cells as part of an autoimmune response to heart attack and that complement factor B protein participates in the formation of the membrane attack complex, which punctures holes in heart cell membranes.
“It was very surprising that heart muscle cells express complement factor B, an immune system protein, because traditionally these cells are known for their contraction function, which supports heart pumping, not as part of the immune response to injury,” notes Dr. Singh. “Clearly, if this immune system response is induced during heart attack injury, it might amplify heart damage by poking holes in the cell membrane. Not only is the heart trying to recover from the injury induced by the heart attack, but it also has to deal with the consequences of the induced activity of the complement pathway, which is attacking the cell membranes.”
In addition, the researchers found that genetically engineered mice that did not express functional complement factor B were partly protected from heart attack, showing reduced mortality and heart damage.
The article was published online March 9 in the Journal of Clinical Investigation.