BMP1-3 antibody prevents fibrosis after acute myocardial infarction (CROSBI ID 615794)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Dumić-Čule, Ivo ; Rogić, Dunja ; Delić-Brkljačić, Diana ; Brkljačić, Boris ; Švarc, Alfred ; Perić, Mihaela ; Grgurević, Lovorka ; Vukičević, Slobodan
engleski
BMP1-3 antibody prevents fibrosis after acute myocardial infarction
Although effective therapies for halting progression of cardiac fibrosis and stimulating heart regeneration following acute myocardial infarction (AMI) have been thoroughly investigated in the past decades, options to reverse the deposition of poor quality fibrotic tissue have remained limited. The transmural infarct scar following AMI was recognized as a living tissue composed of myofibroblasts depositing type I and III fibrillar collagens. We hypothesized that their maturation and crosslinking is possibly mediated by BMP1 isoforms proteolytic activity, which are matrix metalloproteinases. We identified BMP1 isoforms of the Bmp1 gene in the plasma of healthy volunteers and patients with AMI. Bmp1-3 expression was upregulated in human heart sections from patients with AMI. We developed and administered specific BMP1-3 monoclonal antibody to rats with AMI and demonstrated significantly lower concentration of heart enzymes (troponin t, CK-MB) in the plasma of treated rats. The histological analysis of the heart muscle showed that BMP1-3 antibody significantly decreased the size of the scar and modulate its composition. The echocardiographic analyses showed that 45 days after the ligation the ejection fraction in rats treated with the antibody was 25% higher than in control rats, thus revealing significantly reduced level of heart fibrosis. PET scan of the heart was performed before, immediately after and 1 month after AMI to determine the fluorodeoxyglucose (FDG) uptake differences. Decreased FDG uptake due to AMI was partially restored by BMP1-3 therapy. Targeting specific BMP1 isoforms as mediators of heart fibrosis may offer a new therapeutic approach for reducing progression of AMI related scarring.
acute myocardial infarcion; BMP1-3 antibody; fibrosis
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Podaci o prilogu
2014.
objavljeno
Podaci o matičnoj publikaciji
10. Conference on Bone Morphogenetic Proteins, book of abstracts
Podaci o skupu
10. Conference on Bone Morphogenetic Proteins
poster
16.09.2014-20.09.2014
Berlin, Njemačka