心血管异位钙化发病机制的研究进展
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摘要
心血管异位钙化是一种与临床多种心血管事件密切相关的病理改变,是发生恶性事件的独立危险因素,其发生进展是类似骨重塑的主动而复杂的过程,其中包括血管平滑肌、间质细胞及基质细胞的参与,多种细胞因子及介质、外泌因子的调节以及脂肪酸代谢、炎性反应的干预等多因素共同作用。了解其发病机制对于预防及阻断其进展、维护老年人生命健康、降低老年人群的死亡率有着重要意义。
Cardiovascular ectopic calcification is a pathological change closely related to clinical events and an independent risk factor of malignant cardiovascular events, its occurrence and development is an active and complex process similar to bone remodeling, including the participation of vascular smooth muscle, interstitial cell, stroma cell, the adjustment of varieties of cytokines, medium and eccrine factors, and the combined action of multiple factors, such as the intervention of fatty acid metabolism and inflammatory reaction. It has great significance of understanding its pathogenesis for preventing and stopping its progress, maintaining elderly life health, and decreasing the mortality rate of the elderly people.
Cardiovascular ectopic calcification is a pathological change closely related to clinical events and an independent risk factor of malignant cardiovascular events, its occurrence and development is an active and complex process similar to bone remodeling, including the participation of vascular smooth muscle, interstitial cell, stroma cell, the adjustment of varieties of cytokines, medium and eccrine factors, and the combined action of multiple factors, such as the intervention of fatty acid metabolism and inflammatory reaction. It has great significance of understanding its pathogenesis for preventing and stopping its progress, maintaining elderly life health, and decreasing the mortality rate of the elderly people.
引文
[1]陈宇,王士雯.心血管系统异位钙化分子研究进展[J].心血管病学进展,2004,25(2):81-84.
[2]Kim JH,Choi YK,Do JY,et al.Estrogen-Related Receptor gamma Plays a Key Role in Vascular Calcification Through the Up-regulation of BMP2 Expression[J].Arterioscler Thromb Vasc Biol,2015,35(11):2384-2390.
[3]Davaine JM,Quillard T,Chatelais M,et al.Bone Like Arterial Calcification in Femoral Atherosclerotic Lesions:Prevalence and Role of Osteoprotegerin and Pericytes[J].Eur J Vasc Endovasc Surg,2016,51(2):259-267.
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[5]Graham G,Michael JB,Matthew J,et al.Impact of coronary artery calcification on all-cause mortality in individuals with and without hypertension[J].Atherosclerosis,2012,225(2):432-437.
[6]Bostrom KI.Where do we stand on vascular calcification?[J].Vascul Pharmacol,2016,84(9):8-14.
[7]New SE,Aikawa E.Cardiovascular calcification:an inflammatory disease[J].Circ J,2011,75(6):1305-1313.
[8]Haussler MR,Whitfield GK,Haussler CA,et al.1,25-Dihydroxyvitamin D and Klotho:A Tale of Two Renal Hormones Coming of Age[J].Vitam Horm,2016,100(1):165-230.
[9]Mari C,Kazuhiko S.Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves[J].J Pharmacol Sci,2018,136(1):257-265.
[10]Schurgers LJ,Teunissen KJ,Knapen MH,et al.Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid(Gla)protein:under carboxylated matrix Gla protein as marker for vascular calcification[J].Arterioscler Thromb Vasc Biol,2005,25(8):1629-1633.
[11]Goettsch C,Hutcheson JD,Aikawa M,et al.Sortilin mediates vascular calcification via its recruitment into extracellular vesicles[J].Clin Invest,2016,126(4):1323-1336.
[12]Chang JC,Miura RM.Regulatory inhibition of biological tissue mineralization by calcium phosphate through postnucleation shielding by fetuin-A[J].J Chem Phys,2016,144(15):154906.
[13]Speer MY,Giachelli CM.Regulation of cardiovascular calcification[J].Cardiovasc athol,2004,13(2):63-70.
[14]Chen NX,Moe SM.Pathophysiology of Vascular Calcification[J].Curr Osteoporos Rep,2015,13(5):372-380.
[15]Fukumoto S.Vascular Calcification Pathological Mechanism and Clinical Application.Regulation of mineral metabolism and mineralization by FGF-23[J].Clin Alcium,2015,2(5):687-691.
[16]Ragnauth CD,Warren DT.Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging[J].Circulation,2010,121(20):2200-2210.
[17]Chen JH,Yip CY,Sone ED,et al.Identification and characterization of aortic valve mesenchymal progenitor cells with robust osteogenic calcification potential[J].Am JPathol,2009,174(3):1109-1119.
[18]Martinez JM,Mu觡oz-C JR,Herencia C,et al.In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/beta-catenin activation[J].Am J Physiol Renal Physiol,2013,303(8):1136-1144.
[19]Shroff R,Long DA,Shanahan C,et al.Mechanistic insights into vascular calcification in CKD[J].J Am Soc Nephrol,2013,24(2):179-189.
[20]Rong S,Zhao X,Jin X,et al.Vascular calcification in chronic kidney disease is induced by bone orphogenetic protein-2 via a mechanism involving the Wnt/betacatenin pathway[J].Cell Physiol Biochem,2014,34(6):2049-2060.
[21]Yao L,Sun YT,Sun W,et al.High phosphorus level leads to aortic calcification via beta-catenin in chronic kidney disease[J].Am J Nephrol,2015,41(1):28-36.
[22]Alesutan I,Musculus K,Castor T,et al.Inhibition of Phosphate-Induced Vascular Smooth Muscle Cell Osteo-/Chondrogenic Signaling and Calcification by Bafilomycin A1 and Methylamine[J].Kidney Blood Press Res,2015,40(5):490-499.
[23]Husseini ED,Boulanger MC,Mahmut A,et al.P2Y2 receptor represses IL-6 expression by valve intertstitial cells through Akt:implication for calcific aortic valve disease[J].J Mol Cell Cardiol,2014,72(6):146-156.
[24]Vorkas PA,Isaac G,Holmgren A,et al.Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease:An exploratory lipidomic study[J].Int J Cardiol,2015,197(10):192-199.
[25]Rizza S,Copetti M,Rossi C,et al.Meta-bolomics signature improves the prediction of cardiovascular events in elderly subjects[J].Atherosclerosis,2014,232(2):260-264.
[26]Huang CC,McDermott MM,Liu K,et al.Plasma metabolomics profiles predict near-term death among individuals with lower extremity peripheral arterial disease[J].Vasc Surg,2013,58(4):989-996.
[27]Kapustin AN,Davies JD,Reynolds JL,et al.Calcium regulates key components of vascular smooth muscle cellderived matrix vesicles to enhance mineralization[J].Circ Res,2011,109(1):1-12.
[28]Schlieper G,Aretz A,Verberckmoes SC,et al.Ultrastructural analysis of vascular calcifications in uremia[J].JAm Soc Nephrol,2010,21(4):689-696.
[29]New SE,Goettsch C,Aikawa M,et al.Macrophage-derived matrix vesicles:an alternative novel mechanism for microcalcification in atherosclerotic plaques[J].Circ Res,2013,113(1):72-77.
[30]Bertazzo S,Gentleman E,Cloyd KL,et al.Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification[J].Nat Mater,2013,12(6):576-583.
[31]Kapustin AN,Chatrou ML,Drozdov I,et al.Vascular Smooth Muscle Cell Calcification Is Mediated by Regulated Exosome Secretion[J].Circ Res,2015,116(8):1312-1323.
[32]Shroff RC,McNair R,Figg N,et al.Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis[J].Circulation,2008,118(17):1748-1757.
[33]Agharazii M,St-Louis R,Gautier BA,et al.Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease related vascular calcification[J].Am J Hypertens,2015,28(6):746-755.
[34]Buendia P,Montesde OA,Madueno JA,et al.Endothelial microparticles mediate inflammation induced vascular calcification[J].FASEB J,2015,29(1):173-181.
[35]Abdelbaky A,Corsini E,Figueroa AL,et al.Early aortic valve inflammation precedes calcification:a longitudinal FDG-PET/CT study[J].Atherosclerosis,2015,238(2):165-172.
[36]Hofmann Bowman MA,Gawdzik J,Bukhari U,et al.S100A12in vascular smooth muscle accelerates vascular calcification in apolipoprotein E-null mice by activating an osteogenic gene regulatory program[J].Arterioscler Thromb Vasc Biol,2011,31(2):337-344.
[37]Chen Q,Wang ZY.Roles of High Mobility Group Box 1 inCardiovascular Calcification[J].Cell Physiol Biochem,2017,42(2):427-440.
[2]Kim JH,Choi YK,Do JY,et al.Estrogen-Related Receptor gamma Plays a Key Role in Vascular Calcification Through the Up-regulation of BMP2 Expression[J].Arterioscler Thromb Vasc Biol,2015,35(11):2384-2390.
[3]Davaine JM,Quillard T,Chatelais M,et al.Bone Like Arterial Calcification in Femoral Atherosclerotic Lesions:Prevalence and Role of Osteoprotegerin and Pericytes[J].Eur J Vasc Endovasc Surg,2016,51(2):259-267.
[4]Brinda AT,Ikeda K,Hirata KI,et al.Macrophages Highly Express Carbonic Anhydrase 2 and Play a Significant Role in Demineralization of the Ectopic Calcification[J].Kobe J Med Sci,2017,63(2):45-50.
[5]Graham G,Michael JB,Matthew J,et al.Impact of coronary artery calcification on all-cause mortality in individuals with and without hypertension[J].Atherosclerosis,2012,225(2):432-437.
[6]Bostrom KI.Where do we stand on vascular calcification?[J].Vascul Pharmacol,2016,84(9):8-14.
[7]New SE,Aikawa E.Cardiovascular calcification:an inflammatory disease[J].Circ J,2011,75(6):1305-1313.
[8]Haussler MR,Whitfield GK,Haussler CA,et al.1,25-Dihydroxyvitamin D and Klotho:A Tale of Two Renal Hormones Coming of Age[J].Vitam Horm,2016,100(1):165-230.
[9]Mari C,Kazuhiko S.Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves[J].J Pharmacol Sci,2018,136(1):257-265.
[10]Schurgers LJ,Teunissen KJ,Knapen MH,et al.Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid(Gla)protein:under carboxylated matrix Gla protein as marker for vascular calcification[J].Arterioscler Thromb Vasc Biol,2005,25(8):1629-1633.
[11]Goettsch C,Hutcheson JD,Aikawa M,et al.Sortilin mediates vascular calcification via its recruitment into extracellular vesicles[J].Clin Invest,2016,126(4):1323-1336.
[12]Chang JC,Miura RM.Regulatory inhibition of biological tissue mineralization by calcium phosphate through postnucleation shielding by fetuin-A[J].J Chem Phys,2016,144(15):154906.
[13]Speer MY,Giachelli CM.Regulation of cardiovascular calcification[J].Cardiovasc athol,2004,13(2):63-70.
[14]Chen NX,Moe SM.Pathophysiology of Vascular Calcification[J].Curr Osteoporos Rep,2015,13(5):372-380.
[15]Fukumoto S.Vascular Calcification Pathological Mechanism and Clinical Application.Regulation of mineral metabolism and mineralization by FGF-23[J].Clin Alcium,2015,2(5):687-691.
[16]Ragnauth CD,Warren DT.Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging[J].Circulation,2010,121(20):2200-2210.
[17]Chen JH,Yip CY,Sone ED,et al.Identification and characterization of aortic valve mesenchymal progenitor cells with robust osteogenic calcification potential[J].Am JPathol,2009,174(3):1109-1119.
[18]Martinez JM,Mu觡oz-C JR,Herencia C,et al.In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/beta-catenin activation[J].Am J Physiol Renal Physiol,2013,303(8):1136-1144.
[19]Shroff R,Long DA,Shanahan C,et al.Mechanistic insights into vascular calcification in CKD[J].J Am Soc Nephrol,2013,24(2):179-189.
[20]Rong S,Zhao X,Jin X,et al.Vascular calcification in chronic kidney disease is induced by bone orphogenetic protein-2 via a mechanism involving the Wnt/betacatenin pathway[J].Cell Physiol Biochem,2014,34(6):2049-2060.
[21]Yao L,Sun YT,Sun W,et al.High phosphorus level leads to aortic calcification via beta-catenin in chronic kidney disease[J].Am J Nephrol,2015,41(1):28-36.
[22]Alesutan I,Musculus K,Castor T,et al.Inhibition of Phosphate-Induced Vascular Smooth Muscle Cell Osteo-/Chondrogenic Signaling and Calcification by Bafilomycin A1 and Methylamine[J].Kidney Blood Press Res,2015,40(5):490-499.
[23]Husseini ED,Boulanger MC,Mahmut A,et al.P2Y2 receptor represses IL-6 expression by valve intertstitial cells through Akt:implication for calcific aortic valve disease[J].J Mol Cell Cardiol,2014,72(6):146-156.
[24]Vorkas PA,Isaac G,Holmgren A,et al.Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease:An exploratory lipidomic study[J].Int J Cardiol,2015,197(10):192-199.
[25]Rizza S,Copetti M,Rossi C,et al.Meta-bolomics signature improves the prediction of cardiovascular events in elderly subjects[J].Atherosclerosis,2014,232(2):260-264.
[26]Huang CC,McDermott MM,Liu K,et al.Plasma metabolomics profiles predict near-term death among individuals with lower extremity peripheral arterial disease[J].Vasc Surg,2013,58(4):989-996.
[27]Kapustin AN,Davies JD,Reynolds JL,et al.Calcium regulates key components of vascular smooth muscle cellderived matrix vesicles to enhance mineralization[J].Circ Res,2011,109(1):1-12.
[28]Schlieper G,Aretz A,Verberckmoes SC,et al.Ultrastructural analysis of vascular calcifications in uremia[J].JAm Soc Nephrol,2010,21(4):689-696.
[29]New SE,Goettsch C,Aikawa M,et al.Macrophage-derived matrix vesicles:an alternative novel mechanism for microcalcification in atherosclerotic plaques[J].Circ Res,2013,113(1):72-77.
[30]Bertazzo S,Gentleman E,Cloyd KL,et al.Nano-analytical electron microscopy reveals fundamental insights into human cardiovascular tissue calcification[J].Nat Mater,2013,12(6):576-583.
[31]Kapustin AN,Chatrou ML,Drozdov I,et al.Vascular Smooth Muscle Cell Calcification Is Mediated by Regulated Exosome Secretion[J].Circ Res,2015,116(8):1312-1323.
[32]Shroff RC,McNair R,Figg N,et al.Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis[J].Circulation,2008,118(17):1748-1757.
[33]Agharazii M,St-Louis R,Gautier BA,et al.Inflammatory cytokines and reactive oxygen species as mediators of chronic kidney disease related vascular calcification[J].Am J Hypertens,2015,28(6):746-755.
[34]Buendia P,Montesde OA,Madueno JA,et al.Endothelial microparticles mediate inflammation induced vascular calcification[J].FASEB J,2015,29(1):173-181.
[35]Abdelbaky A,Corsini E,Figueroa AL,et al.Early aortic valve inflammation precedes calcification:a longitudinal FDG-PET/CT study[J].Atherosclerosis,2015,238(2):165-172.
[36]Hofmann Bowman MA,Gawdzik J,Bukhari U,et al.S100A12in vascular smooth muscle accelerates vascular calcification in apolipoprotein E-null mice by activating an osteogenic gene regulatory program[J].Arterioscler Thromb Vasc Biol,2011,31(2):337-344.
[37]Chen Q,Wang ZY.Roles of High Mobility Group Box 1 inCardiovascular Calcification[J].Cell Physiol Biochem,2017,42(2):427-440.