BMP1 5'UTR + 104 T/C gene variation: can be a predictive marker for serum HDL and apoprotein A1 levels in male patients with coronary heart disease.

Apolipoprotein A1 (Apo A1), the major protein of HDL, is secreted as a proprotein and then is cleaved by C-terminal procollagen endoproteinase/bone morphogenetic protein-1 (BMP1). BMP1 stimulates the conversion of newly secreted proapo A1 to its phospholipid-binding form. Therefore, genetic variations of BMP1 gene may affect serum ApoA1 and HDL levels. We aimed to investigate the effects of the functional 5'UTR + 104 (T/C) variant of BMP1 on serum ApoA1 and HDL levels and risk of coronary heart disease (CHD) in this study. The BMP1 5'UTR + 104 (T/C) (rs143383) variation was determined in 131 male patients with CHD and 51 male controls by real-time polymerase chain reaction technique. ApoA1 levels were measured by immunoturbidimetry. The serum Apo-A1 levels were found higher in controls with the BMP1-CC genotype than those with the T-allele (p < 0.001). Our findings show the association of this variation with serum ApoA1 and HDL-C levels which increase in the order of CT < TT < CC in the controls. No effect was found on ApoA1 and HDL-C levels in CHD patients, as it was observed in the controls. However, the BMP1-TT genotype was associated with higher triglyceride (TG) levels as compared to C-allele (p = 0.009). These discrepancies could be due to statin therapy which has dominant effects on lowering cholesterol levels comparing to TG levels. Our results indicated that the BMP1 5'UTR + 104 (T/C) variation may affect the serum ApoA1 and lipoprotein levels depending on statin therapy so that contributes to the development of CHD.

The diagnostic role of signal peptide-C1r/C1s, Uegf, and Bmp1-epidermal growth factor domain-containing protein 1 in non-ST-elevation acute coronary syndrome.

OBJECTIVE: Chest pain and/or electrocardiogram changes in non-ST elevation or suspicious chest pain and cardiac marker elevations are defined as non-ST-elevation acute coronary syndrome (NSTE-ACS). Serial electrocardiogram and marker follow-up are needed to make a diagnosis of NSTE-ACS and to eliminate noncoronary chest pain (NCCP). Signal peptide-C1r/C1s, Uegf, and Bmp1-epidermal growth factor domain-containing protein 1 (SCUBE1) is stored within the α granules of inactive platelets and secreted at a high rate during thrombosis. We believe that SCUBE1 may be a sensitive early diagnostic indicator in distinguishing coronary-induced chest pain from noncoronary-induced chest pain. MATERIALS AND METHODS: The study included 190 patients with an initial diagnosis of acute coronary syndrome in the emergency department. Based on a definitive diagnosis, these patients were classified into 3 groups: ST-elevation myocardial infarction (STEMI), NSTE-ACS, and NCCP. RESULTS: Plasma SCUBE1 levels were significantly higher in the STEMI group when compared with those of the other groups (P < .05). They were also significantly higher in the NSTE-ACS group when compared with those of the NCCP group (P < .01). Troponin I, creatinine kinase, and creatinine kinase MB levels were significantly different in the NSTE-ACS group when compared with those of the NCCP group (P < .05). CONCLUSION: High rates of SCUBE1 were found both in the STEMI and NSTE-ACS patients. Furthermore, in the study group, SCUBE1 was an adequate marker for distinguishing NSTE-ACS from NCCP.

Circulating bone morphogenetic protein 1-3 isoform increases renal fibrosis.

Bone morphogenetic proteins (BMPs) participate in organ regeneration through autocrine and paracrine actions, but the existence and effects of these proteins in the systemic circulation is unknown. Using liquid chromatography-mass spectrometry, we identified BMP6, GDF15, and the BMP1-3 isoform of the Bmp1 gene in plasma samples from healthy volunteers and patients with CKD. We isolated the endogenous BMP1-3 protein and demonstrated that it circulates as an active enzyme, evidenced by its ability to cleave dentin matrix protein-1 in vitro. In rats with CKD, administration of recombinant BMP1-3 increased renal fibrosis and reduced survival. In contrast, administration of a BMP1-3-neutralizing antibody reduced renal fibrosis, preserved renal function, and increased survival. In addition, treating with the neutralizing antibody was associated with low plasma levels of TGFß1 and connective tissue growth factor. In HEK293 cells and remnant kidneys, BMP1-3 increased the transcription of collagen type I, TGFß1, ß-catenin, and BMP7 via a BMP- and Wnt-independent mechanism that involved signaling through an integrin ß1 subunit. The profibrotic effect of BMP1-3 may, in part, be a result of the accompanied decrease in decorin (DCN) expression. Taken together, inhibition of circulating BMP1-3 reduces renal fibrosis, suggesting that this pathway may be a therapeutic target for CKD.