骨钙素与血管钙化——从临床到分子
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摘要
血管钙化是心血管疾病发病和死亡的主要危险因素,也是全因死亡的一个重要因素。骨钙素是由成骨细胞产生的一种激素,其不仅参与骨形成,而且在钙化血管中普遍存在,在血管钙化过程中扮演着重要的角色,但其具体作用尚未完全阐明。现综述骨钙素与血管钙化关系及相关分子机制。
Vascular calcification is a major risk factor of cardiovascular disease and mortality,and it is also an important factor in allcause mortality. Osteocalcin is a hormone produced by osteoblasts. It not only participates in bone formation,but also exists in calcified blood vessels. It plays an important role in the process of vascular calcification,but the specific role has not been fully elucidated. This review focuses on the relationship between osteocalcin and vascular calcification and related molecular mechanisms.
Vascular calcification is a major risk factor of cardiovascular disease and mortality,and it is also an important factor in allcause mortality. Osteocalcin is a hormone produced by osteoblasts. It not only participates in bone formation,but also exists in calcified blood vessels. It plays an important role in the process of vascular calcification,but the specific role has not been fully elucidated. This review focuses on the relationship between osteocalcin and vascular calcification and related molecular mechanisms.
引文
[1]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2016》概要[J].中国循环杂志,2017,32(6):521-530.
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[3]Oikonomou E,Siasos G,Georgiopoulos G,et al.Arterial stiffness and vascular calcification predicts adverse cardiovascular events in subjects with coronary artery disease after percutaneous coronary intervention[J].J Am Coll Cardiol,2018,71(11):109-117.
[4]Levine GN,Bates ER,Blankenship JC,et al.2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention:executive summary:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions[J].Circulation,2011,124(23):2574-2609.
[5]Millar SA,Patel H,Anderson SI,et al.Osteocalcin,vascular calcification,and atherosclerosis:a systematic review and meta-analysis[J].Front Endocrinol,2017,8(6):183.
[6]Spence LA,Weaver CM.Calcium intake,vascular calcification,and vascular disease[J].Nutr Rev,2013,71(1):15-22.
[7]Maldonado N,Kelly-Arnold A,Cardoso L,et al.The explosive growth of small voids in vulnerable cap rupture;cavitation and interfacial debonding[J].J Biomech,2013,46(2):396-401.
[8]Chang X,Lihua LI,Zhang B,et al.Regulatory mechanism of vascular calcification and its smooth muscle cell phenotype transformation[J].China Med Herald,2016,5(6):36-39.
[9]Hauschka PV,Lian JB,Gallop PM,et al.Direct identification of the calciumbinding amino acid,gamma-carboxyglutamate,in mineralized tissue[J].Proc Natl Acad Sci USA,1975,72(10):3925-3929.
[10]Malashkevich VN,Almo SC,Dowd TL,et al.X-ray crystal structure of bovine 3Glu-osteocalcin[J].Biochemistry,2013,52(47):8387-8392.
[11]Li J,Zhang H,Yang C,et al.An overview of osteocalcin progress[J].J Bone Miner Metab,2016,34(4):367-379.
[12]Hauschka PV,Carr SA.Calcium-dependent alpha-helical structure in osteocalcin[J].Biochemistry,1982,21(10):2538-2547.
[13]Neve A,Corrado A,Cantatore FP.Osteoblast physiology in normal and pathological conditions[J].Cell Tissue Res,2011,343(2):289-302.
[14]Idelevich A,Rais Y,Monsonegoornan E,et al.Bone Gla protein increases HIF-1alpha-dependent glucose metabolism and induces cartilage and vascular calcification[J].Bone,2011,48(9):55-71.
[15]Zhang H,Wang LJ,Si DL,et al.Correlation between osteocalcin-positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease[J].Clin Exp Pharmacol Physiol,2015,42(7):734-739.
[16]Flammer AJ,G9ssl M,Widmer RJ,et al.Osteocalcin positive CD133+/CD34-/KDR+progenitor cells as an independent marker for unstable atherosclerosis[J].Eur Heart J,2012,33(23):2963-2969.
[17]Confavreux CB,Szulc P,Casey R,et al.Higher serum osteocalcin is associated with lower abdominal aortic calcification progression and longer 10-year survival in elderly men of the MINOS cohort[J].J Clin Endocrinol Metab,2013,98(3):1084-1092.
[18]Yamashita T,Okano K,Tsuruta Y,et al.Serum osteocalcin levels are useful as a predictor of cardiovascular events in maintenance hemodialysis patients[J].Int Urol Nephrol,2013,45(1):207-214.
[19]Araldi E,Schipani E.Hypoxia,HIFs and bone development[J].Bone,2010,47(2):190-196.
[20]Li G,Lu W,Ai R,et al.The relationship between serum hypoxia-inducible factor 1αand coronary artery calcification in asymptomatic type 2 diabetic patients[J].Cardiovasc Diabetol,2014,13(1):52-56.
[21]Mokas S,Larivière R,Lamalice L,et al.Hypoxia-inducible factor-1 plays a role in phosphate-induced vascular smooth muscle cell calcification[J].Kidney Int,2016,90(3):598-609.
[22]Komori T.Runx2,an inducer of osteoblast and chondrocyte differentiation[J].Histochem Cell Biol,2018,149(4):313-323.
[23]Cai Y,Wang XL,Flores AM,et al.Inhibition of endo-lysosomal function exacerbates vascular calcification[J].Sci Rep,2018,8(1):3377.
[24]Lin ME,Chen TM,Wallingford MC,et al.Runx2 deletion in smooth muscle cells inhibits vascular osteochondrogenesis and calcification but not atherosclerotic lesion formation[J].Cardiovasc Res,2016,112(2):606-616.
[25]Byon CH,Javed A,Dai Q,et al.Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling[J].J Biol Chem,2008,283(22):15319-15327.
[26]Galvin KM,Donovan MJ,Lvnch CA,et al.A role for smad6 in development and homeostasis of the cardiovascular system[J].Nat Genet,2000,24(2):171-174.
[27]Qin CM,Wei X,Gong CP,et al.Expression of BMP2/Smad1/Runx2 signal pathway in renal artery of rat with vascular calcification[J].Sichunan Da Xue Xue Bao Yi Xue Ban,2016,47(2):180-183.
[28]Rong S,Zhao X,Jin X,et al.Vascular calcification in chronic kidney disease is induced by bone morphogenetic protein-2 via a mechanism involving the Wnt/β-catenin pathway[J].Cell Physiol Biochem,2014,34(6):2049-2060.
[29]Malhotra R,Burke MF,Martyn T,et al.Inhibition of bone morphogenetic protein signal transduction prevents the medial vascular calcification associated with matrix Gla protein deficiency[J].PLoS One,2015,10(1):e0117098.
[30]Jang WG,Kim EJ,Kim DK,et al.BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription[J].J Biol Chem,2012,287(2):905-915.
[31]Marulanda J,Gao C,Roman H,et al.Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice[J].Bone,2013,57(2):499-508.
[32]Chiyoya M,Seya K,Yu Z,et al.Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves[J].J Pharmacol Sci,2018,136(4):257-265.
[33]Cancela ML,LaizéV,Concei2o N.Matrix Gla protein and osteocalcin:from gene duplication to neofunctionalization[J].Arch Biochem Biophys,2014,561:56-63.
[2]Mc Carty MF,Dinicolantonio JJ.The molecular biology and pathophysiology of vascular calcification[J].Postgrad Med,2014,126(2):54-64.
[3]Oikonomou E,Siasos G,Georgiopoulos G,et al.Arterial stiffness and vascular calcification predicts adverse cardiovascular events in subjects with coronary artery disease after percutaneous coronary intervention[J].J Am Coll Cardiol,2018,71(11):109-117.
[4]Levine GN,Bates ER,Blankenship JC,et al.2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention:executive summary:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions[J].Circulation,2011,124(23):2574-2609.
[5]Millar SA,Patel H,Anderson SI,et al.Osteocalcin,vascular calcification,and atherosclerosis:a systematic review and meta-analysis[J].Front Endocrinol,2017,8(6):183.
[6]Spence LA,Weaver CM.Calcium intake,vascular calcification,and vascular disease[J].Nutr Rev,2013,71(1):15-22.
[7]Maldonado N,Kelly-Arnold A,Cardoso L,et al.The explosive growth of small voids in vulnerable cap rupture;cavitation and interfacial debonding[J].J Biomech,2013,46(2):396-401.
[8]Chang X,Lihua LI,Zhang B,et al.Regulatory mechanism of vascular calcification and its smooth muscle cell phenotype transformation[J].China Med Herald,2016,5(6):36-39.
[9]Hauschka PV,Lian JB,Gallop PM,et al.Direct identification of the calciumbinding amino acid,gamma-carboxyglutamate,in mineralized tissue[J].Proc Natl Acad Sci USA,1975,72(10):3925-3929.
[10]Malashkevich VN,Almo SC,Dowd TL,et al.X-ray crystal structure of bovine 3Glu-osteocalcin[J].Biochemistry,2013,52(47):8387-8392.
[11]Li J,Zhang H,Yang C,et al.An overview of osteocalcin progress[J].J Bone Miner Metab,2016,34(4):367-379.
[12]Hauschka PV,Carr SA.Calcium-dependent alpha-helical structure in osteocalcin[J].Biochemistry,1982,21(10):2538-2547.
[13]Neve A,Corrado A,Cantatore FP.Osteoblast physiology in normal and pathological conditions[J].Cell Tissue Res,2011,343(2):289-302.
[14]Idelevich A,Rais Y,Monsonegoornan E,et al.Bone Gla protein increases HIF-1alpha-dependent glucose metabolism and induces cartilage and vascular calcification[J].Bone,2011,48(9):55-71.
[15]Zhang H,Wang LJ,Si DL,et al.Correlation between osteocalcin-positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease[J].Clin Exp Pharmacol Physiol,2015,42(7):734-739.
[16]Flammer AJ,G9ssl M,Widmer RJ,et al.Osteocalcin positive CD133+/CD34-/KDR+progenitor cells as an independent marker for unstable atherosclerosis[J].Eur Heart J,2012,33(23):2963-2969.
[17]Confavreux CB,Szulc P,Casey R,et al.Higher serum osteocalcin is associated with lower abdominal aortic calcification progression and longer 10-year survival in elderly men of the MINOS cohort[J].J Clin Endocrinol Metab,2013,98(3):1084-1092.
[18]Yamashita T,Okano K,Tsuruta Y,et al.Serum osteocalcin levels are useful as a predictor of cardiovascular events in maintenance hemodialysis patients[J].Int Urol Nephrol,2013,45(1):207-214.
[19]Araldi E,Schipani E.Hypoxia,HIFs and bone development[J].Bone,2010,47(2):190-196.
[20]Li G,Lu W,Ai R,et al.The relationship between serum hypoxia-inducible factor 1αand coronary artery calcification in asymptomatic type 2 diabetic patients[J].Cardiovasc Diabetol,2014,13(1):52-56.
[21]Mokas S,Larivière R,Lamalice L,et al.Hypoxia-inducible factor-1 plays a role in phosphate-induced vascular smooth muscle cell calcification[J].Kidney Int,2016,90(3):598-609.
[22]Komori T.Runx2,an inducer of osteoblast and chondrocyte differentiation[J].Histochem Cell Biol,2018,149(4):313-323.
[23]Cai Y,Wang XL,Flores AM,et al.Inhibition of endo-lysosomal function exacerbates vascular calcification[J].Sci Rep,2018,8(1):3377.
[24]Lin ME,Chen TM,Wallingford MC,et al.Runx2 deletion in smooth muscle cells inhibits vascular osteochondrogenesis and calcification but not atherosclerotic lesion formation[J].Cardiovasc Res,2016,112(2):606-616.
[25]Byon CH,Javed A,Dai Q,et al.Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling[J].J Biol Chem,2008,283(22):15319-15327.
[26]Galvin KM,Donovan MJ,Lvnch CA,et al.A role for smad6 in development and homeostasis of the cardiovascular system[J].Nat Genet,2000,24(2):171-174.
[27]Qin CM,Wei X,Gong CP,et al.Expression of BMP2/Smad1/Runx2 signal pathway in renal artery of rat with vascular calcification[J].Sichunan Da Xue Xue Bao Yi Xue Ban,2016,47(2):180-183.
[28]Rong S,Zhao X,Jin X,et al.Vascular calcification in chronic kidney disease is induced by bone morphogenetic protein-2 via a mechanism involving the Wnt/β-catenin pathway[J].Cell Physiol Biochem,2014,34(6):2049-2060.
[29]Malhotra R,Burke MF,Martyn T,et al.Inhibition of bone morphogenetic protein signal transduction prevents the medial vascular calcification associated with matrix Gla protein deficiency[J].PLoS One,2015,10(1):e0117098.
[30]Jang WG,Kim EJ,Kim DK,et al.BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription[J].J Biol Chem,2012,287(2):905-915.
[31]Marulanda J,Gao C,Roman H,et al.Prevention of arterial calcification corrects the low bone mass phenotype in MGP-deficient mice[J].Bone,2013,57(2):499-508.
[32]Chiyoya M,Seya K,Yu Z,et al.Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves[J].J Pharmacol Sci,2018,136(4):257-265.
[33]Cancela ML,LaizéV,Concei2o N.Matrix Gla protein and osteocalcin:from gene duplication to neofunctionalization[J].Arch Biochem Biophys,2014,561:56-63.