Immune System Cells, Heart Failure Link Found

Researchers from Baylor College of Medicine have found that the immune system and certain cells recruited from it play a major role in the muscle dysfunction that leads to certain forms of heart failure. Report of the study appears online in the Proceedings of the National Academy of Sciences.

The study was conducted by Dr. Mark Entman, Professor of Medicine at BCM as well as Scientific Director of the DeBakey Heart Center, and his colleague Dr. Sandra Haudek, instructor in the same section. The duo used mice that were subjected to short, daily occlusion of the left anterior coronary artery for their research.

While the short occlusions did not lead to any cardiac cell damage, they did result in inappropriate deposition of fibrous tissue in the heart. Over time such deposition weakens the left ventricle, the main pumping chamber of the heart.

“This mimics a disorder seen in patients,” said Dr. Entman. “The mice develop a cardiomyopathy (a disorder of the heart muscle) resulting from coronary insufficiency that is very similar to that seen in clinical coronary disease.”

Study revealed that levels of a particular immune system protein called monocyte chemoattractant protein – 1, or MCP-1 were elevated in both the experimental mice and human patients with the same condition. MCP-1 attracts immune system cells called monocytes to the site of the heart muscle injury. Dr. Entman and his team found that the cells that were attracted to the injury site turned into fibroblasts that not only grew quickly but were also smaller and more spindle-shaped than the regular ones.

When normal, fibroblasts are key players in the wound-healing process. These mutated fibroblasts however cause fibrosis or excess fibrous tissue in the heart muscle. The excess tissue stopped the heart from doing its job and led to cardiomyopathy. The unusual thing about these fibroblasts is that they originate from stem cells that are usually progenitors of blood-related cells or hematopoietic cells.

A second part of the study also revealed a treatment for the condition. The researchers found that treatment with a protein called serum amyloid P (SAP) before and during the period of coronary occlusion arrested the production of the fibroblasts and the resulting fibrosis. They found SAP’s action is on account of its binding to a gamma globulin cellular receptor called Fc gamma.

“Thus, we identified two ways to link cardiac fibrosis to the immune system,” said Dr. Entman. “The monocytes become fibroblasts and the Fc gamma receptor regulates the process. Ischemic cardiomyopathy is the leading cause of death in patients with coronary artery disease. This study suggests some therapeutic targets that might mitigate its progression.”

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