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Researchers at the University of Alberta have discovered a new light on the role of fibrinogen in regulating a body's natural defense mechanism. This discovery should help improve the diagnosis and treatment of patients with various diseases ranging from inflammation to heart failure and cancer.
Fibrinogen is a well-known protein that is essential for healing wounds and coagulating blood in the body. However, a study published in Scientific Reports in March 2019 shows that it is also a natural inhibitor of an enzyme called MMP2, essential for normal development and repair of psoriasis. ; organs.
MMP2 is usually found at increased levels in the blood under pathological conditions. The researchers believe that one of the vital functions of fibrinogen is to allow or not allow the enzyme to perform its normal functions. However, high levels of fibrinogen may inhibit MMP2 excessively, which could lead to arthritic and cardiac disorders similar to those seen in patients with MMP2 deficiency.
"Whenever there is an infection or injury, fibrinogen can multiply in the blood. So, at this concentration, it would excessively inhibit MMP2, "said Hbadan Sarker, PhD student at the University of Alberta and lead author of the study.
"The binding of fibrinogen in the circulation to the enzymes of MMP2 prevents them from attaching to the target tissues," added Carlos Fernandez-Patron, professor of biochemistry at the University of Alberta, who led this research. "It affects their activity, and we do not know exactly whether it translates into a beneficial or deleterious effect – it is something we need to investigate.
The discovery opens a new window on the inner workings of the MMP family of enzymes. Researchers say that better understanding how RPMs are regulated creates opportunities for future treatments. They also suspect that an abnormal activity of MMP2 could be an undesirable side effect of common medications such as the cholesterol-lowering drug called statins and the antibiotic doxycycline, two drugs known to inhibit MMPs.
The researchers point out that future therapeutic developments must find a balance between MMP levels and their inhibitors, such as fibrinogen, so that the net activity of MMPs in the body remains at near normal levels. "We do not want to inhibit them more than necessary and we do not want their expression to be higher than it should be," said Fernandez-Patron. "It is essential to know how these enzymes are regulated to improve the diagnosis, prognosis and treatment of patients with abnormal levels of MMP2 or fibrinogen."
Reference:
H. Sarker, E. Hardy, A. Haimour, W. Maksymowych, L. D. Botto and C. Fernandez-Patron (2019). Identification of fibrinogen as a natural inhibitor of MMP-2. Scientific Reports, 9 (1), 4340. https://doi.org/10.1038/s41598-019-40983-y
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