Could BMP-2 and BMP-7 be biomarkers of coronary artery disease? A pilot clinical study

Abstract Background Coronary artery calcification (CAC) is utilized as an important tool for the global risk assessment of cardiovascular events in individuals with intermediate risk. BMP-2 is a powerful inducer of bone formation and exposure to BMP-2 in the arteries leads to the loss of vascular smooth muscle cells (VSMC) markers and increase gene expression in favor of osteoblasts. BMP-7 is key factor in the bone and kidney and is suggested as inhibitor of vascular calcification. The main purpose of this clinical study was to find out the correlation between BMP-2 and BMP-7serum concentration and CAC in human for the first time. Methods In this study 84 patients with coronary artery disease who fulfilled inclusion and exclusion criteria, entered the study. For all patients a questionnaire consisting demographic data and traditional cardiovascular risk factors were completed. CT-Angiography was carried out to determine coronary artery calcium score and ELISA method was used for measuring BMP-2 and BMP-7serum concentrations. Results There was a significant positive correlation between BMP-2 serum concentration and total CAC score and also CAC of right coronary artery (RCA), left anterior descending (LAD), circumflex (CX), left main coronary artery (LMCA) (P   0.05). Conclusion Based on our results, we can suggest BMP-2 and BMP-7 serum concentration as a probable biomarker for coronary artery disease. However, more studies with higher sample size are necessary for its confirmation.

[1]  D. Zwolińska,et al.  [Osteopontin (OPN), PDGF-BB (platelet-derived growth factor) and BMP-7 (bone morphogenetic protein) as markers of atherogenesis in children with chronic kidney disease (CKD) treated conservatively--preliminary results]. , 2008, Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego.

[2]  Su‐Li Cheng,et al.  Osteogenic Regulation of Vascular Calcification , 2006, Annals of the New York Academy of Sciences.

[3]  R. Schneider,et al.  Exposure to Uremic Serum Induces a Procalcific Phenotype in Human Mesenchymal Stem Cells , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[4]  Su‐Li Cheng,et al.  Vascular Bmp–Msx2–Wnt Signaling and Oxidative Stress in Arterial Calcification , 2007, Annals of the New York Academy of Sciences.

[5]  M. López-Cabrera Mesenchymal Conversion of Mesothelial Cells Is a Key Event in the Pathophysiology of the Peritoneum during Peritoneal Dialysis , 2014, Advances in medicine.

[6]  Roland Baron,et al.  BMP‐2 Controls Alkaline Phosphatase Expression and Osteoblast Mineralization by a Wnt Autocrine Loop , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  K. Hruska,et al.  BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure. , 2003, Journal of the American Society of Nephrology : JASN.

[8]  Y. Tintut,et al.  Vascular calcification: mechanisms and clinical ramifications. , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[9]  Xianwu Li,et al.  BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. , 2008, Atherosclerosis.

[10]  J. Loscalzo,et al.  Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification. , 2011, Biochemical and biophysical research communications.

[11]  K. Hruska,et al.  Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives. , 2005, Kidney international. Supplement.

[12]  H. Matsubara,et al.  Paracrine Osteogenic Signals via Bone Morphogenetic Protein-2 Accelerate the Atherosclerotic Intimal Calcification In Vivo , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[13]  J. Jin,et al.  Bone morphogenetic protein-7 inhibits vascular calcification induced by high vitamin D in mice. , 2010, The Tohoku journal of experimental medicine.

[14]  R. Blumenthal,et al.  Coronary calcification and coronary heart disease death rates in different countries, not only the influence of classical risk factors. , 2009, Atherosclerosis.

[15]  J. Loscalzo,et al.  Bone Morphogenetic Protein‐2 Decreases MicroRNA‐30b and MicroRNA‐30c to Promote Vascular Smooth Muscle Cell Calcification , 2012, Journal of the American Heart Association.

[16]  G. Stein,et al.  Reconstitution of Runx2/Cbfa1‐null cells identifies a requirement for BMP2 signaling through a Runx2 functional domain during osteoblast differentiation , 2007, Journal of cellular biochemistry.

[17]  E. Aikawa,et al.  Inhibition of Bone Morphogenetic Protein Signaling Reduces Vascular Calcification and Atherosclerosis , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[18]  N. Chen,et al.  The mechanisms of uremic serum-induced expression of bone matrix proteins in bovine vascular smooth muscle cells. , 2006, Kidney international.

[19]  J. Bigby Harrison's Principles of Internal Medicine , 1988 .

[20]  J. Sara,et al.  Increased plasma BMP-2 levels are associated with atherosclerosis burden and coronary calcification in type 2 diabetic patients , 2015, Cardiovascular Diabetology.

[21]  D. Towler,et al.  The regulation of valvular and vascular sclerosis by osteogenic morphogens. , 2011, Circulation research.