Platelets in Vascular Calcification: A Comprehensive Review of Platelet-Derived Extracellular Vesicles, Protein Interactions, Platelet Function Indices, and their Impact on Cellular Crosstalk

Abstract

Vascular calcification (VC) commonly accompanies the development of atherosclerosis, defined by the accumulation of calcium in the arterial wall, potentially leading to stroke and myocardial infarction. Severe and unevenly distributed calcification poses challenges for interventional procedures, elevating the risks of vascular dissection, acute vascular occlusion, restenosis, and other major adverse cardiovascular events. Platelets promote the development of atherosclerosis by secreting various inflammatory mediators, regulating cell migration, aggregation, adhesion, and initiating and expanding inflammatory responses. There is emerging evidence that platelets play a direct role in VC; however, this novel concept has not yet been critically assessed. This review describes the intricate mechanisms by which platelets promote VC, focusing on three key aspects and the potential opportunities for their therapeutic targeting: extracellular vesicles, platelet-regulatory proteins, and indices related to platelet function.

Keywords

platelet - vascular calcification - cellular crosstalk - platelet-derived extracellular vesicles - platelet-derived growth factor-BB

^* These authors contributed equally to this article.

Publikationsverlauf

Artikel online veröffentlicht:
27. August 2024

• References

• 1 Patel JJ, Bourne LE, Davies BK. et al. Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts. Exp Cell Res 2019; 380 (01) 100-113
• 2 London GM, Guérin AP, Marchais SJ, Métivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18 (09) 1731-1740
• 3 Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 2011; 109 (06) 697-711
• 4 Amann K. Media calcification and intima calcification are distinct entities in chronic kidney disease. Clin J Am Soc Nephrol 2008; 3 (06) 1599-1605
• 5 Buffolo F, Monticone S, Camussi G, Aikawa E. Role of extracellular vesicles in the pathogenesis of vascular damage. Hypertension 2022; 79 (05) 863-873
• 6 Yahagi K, Kolodgie FD, Lutter C. et al. Pathology of human coronary and carotid artery atherosclerosis and vascular calcification in diabetes mellitus. Arterioscler Thromb Vasc Biol 2017; 37 (02) 191-204
• 7 Dayawansa NH, Baratchi S, Peter K. Uncoupling the vicious cycle of mechanical stress and inflammation in calcific aortic valve disease. Front Cardiovasc Med 2022; 9: 783543
• 8 Miller JM, Rochitte CE, Dewey M. et al. Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008; 359 (22) 2324-2336
• 9 Théry C, Witwer KW, Aikawa E. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 2018; 7 (01) 1535750
• 10 Boulanger CM, Loyer X, Rautou PE, Amabile N. Extracellular vesicles in coronary artery disease. Nat Rev Cardiol 2017; 14 (05) 259-272
• 11 Bonucci E. Fine structure of early cartilage calcification. J Ultrastruct Res 1967; 20 (01) 33-50
• 12 Schmidt JR, Kliemt S, Preissler C. et al. Osteoblast-released matrix vesicles, regulation of activity and composition by sulfated and non-sulfated glycosaminoglycans. Mol Cell Proteomics 2016; 15 (02) 558-572
• 13 Koga H, Sugiyama S, Kugiyama K. et al. Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2005; 45 (10) 1622-1630
• 14 Sinning JM, Losch J, Walenta K, Böhm M, Nickenig G, Werner N. Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. Eur Heart J 2011; 32 (16) 2034-2041
• 15 Badimon L, Suades R, Arderiu G, Peña E, Chiva-Blanch G, Padró T. Microvesicles in atherosclerosis and angiogenesis: from bench to bedside and reverse. Front Cardiovasc Med 2017; 4: 77
• 16 Mayr M, Grainger D, Mayr U. et al. Proteomics, metabolomics, and immunomics on microparticles derived from human atherosclerotic plaques. Circ Cardiovasc Genet 2009; 2 (04) 379-388
• 17 Merten M, Pakala R, Thiagarajan P, Benedict CR. Platelet microparticles promote platelet interaction with subendothelial matrix in a glycoprotein IIb/IIIa-dependent mechanism. Circulation 1999; 99 (19) 2577-2582
• 18 Min PK, Kim JY, Chung KH. et al. Local increase in microparticles from the aspirate of culprit coronary arteries in patients with ST-segment elevation myocardial infarction. Atherosclerosis 2013; 227 (02) 323-328
• 19 Chironi G, Simon A, Hugel B. et al. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects. Arterioscler Thromb Vasc Biol 2006; 26 (12) 2775-2780
• 20 Chiva-Blanch G, Suades R, Crespo J. et al. CD3(+)/CD45(+) and SMA-α(+) circulating microparticles are increased in individuals at high cardiovascular risk who will develop a major cardiovascular event. Int J Cardiol 2016; 208: 147-149
• 21 Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 2009; 21 (04) 575-581
• 22 Kapustin AN, Chatrou ML, Drozdov I. et al. Vascular smooth muscle cell calcification is mediated by regulated exosome secretion. Circ Res 2015; 116 (08) 1312-1323
• 23 Kapustin AN, Shanahan CM. Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation. J Physiol 2016; 594 (11) 2905-2914
• 24 Tan M, Yan HB, Li JN. et al. thrombin stimulated platelet-derived exosomes inhibit platelet-derived growth factor receptor-beta expression in vascular smooth muscle cells. Cell Physiol Biochem 2016; 38 (06) 2348-2365
• 25 Postea O, Vasina EM, Cauwenberghs S. et al. Contribution of platelet CX(3)CR1 to platelet-monocyte complex formation and vascular recruitment during hyperlipidemia. Arterioscler Thromb Vasc Biol 2012; 32 (05) 1186-1193
• 26 Basatemur GL, Jørgensen HF, Clarke MCH, Bennett MR, Mallat Z. Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol 2019; 16 (12) 727-744
• 27 Vajen T, Benedikter BJ, Heinzmann ACA. et al. Platelet extracellular vesicles induce a pro-inflammatory smooth muscle cell phenotype. J Extracell Vesicles 2017; 6 (01) 1322454
• 28 Gidlöf O, van der Brug M, Ohman J. et al. Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood 2013; 121 (19) 3908-3917 , S1–S26
• 29 Bei JJ, Liu C, Peng S. et al. Staphylococcal SSL5-induced platelet microparticles provoke proinflammatory responses via the CD40/TRAF6/NFκB signalling pathway in monocytes. Thromb Haemost 2016; 115 (03) 632-645
• 30 He S, Wu C, Xiao J, Li D, Sun Z, Li M. Endothelial extracellular vesicles modulate the macrophage phenotype: potential implications in atherosclerosis. Scand J Immunol 2018; 87 (04) e12648
• 31 Sadallah S, Eken C, Martin PJ, Schifferli JA. Microparticles (ectosomes) shed by stored human platelets downregulate macrophages and modify the development of dendritic cells. J Immunol 2011; 186 (11) 6543-6552
• 32 Laffont B, Corduan A, Rousseau M. et al. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost 2016; 115 (02) 311-323
• 33 Oggero S, de Gaetano M, Marcone S. et al. Extracellular vesicles from monocyte/platelet aggregates modulate human atherosclerotic plaque reactivity. J Extracell Vesicles 2021; 10 (06) 12084
• 34 Zhang X, Li J, Qin JJ. et al. Oncostatin M receptor β deficiency attenuates atherogenesis by inhibiting JAK2/STAT3 signaling in macrophages. J Lipid Res 2017; 58 (05) 895-906
• 35 Kraft CT, Agarwal S, Ranganathan K. et al. Trauma-induced heterotopic bone formation and the role of the immune system: a review. J Trauma Acute Care Surg 2016; 80 (01) 156-165
• 36 Vasina EM, Cauwenberghs S, Feijge MA, Heemskerk JW, Weber C, Koenen RR. Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis 2011; 2 (09) e211
• 37 Braga TT, Agudelo JS, Camara NO. Macrophages during the fibrotic process: M2 as friend and foe. Front Immunol 2015; 6: 602
• 38 Diehl P, Fricke A, Sander L. et al. Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res 2012; 93 (04) 633-644
• 39 Laffont B, Corduan A, Plé H. et al. Activated platelets can deliver mRNA regulatory Ago2 microRNA complexes to endothelial cells via microparticles. Blood 2013; 122 (02) 253-261
• 40 Yuan C, Ni L, Zhang C, Hu X, Wu X. Vascular calcification: new insights into endothelial cells. Microvasc Res 2021; 134: 104105
• 41 Kostina A, Semenova D, Kostina D, Uspensky V, Kostareva A, Malashicheva A. Human aortic endothelial cells have osteogenic Notch-dependent properties in co-culture with aortic smooth muscle cells. Biochem Biophys Res Commun 2019; 514 (02) 462-468
• 42 Santilli F, Basili S, Ferroni P, Davì G. CD40/CD40L system and vascular disease. Intern Emerg Med 2007; 2 (04) 256-268
• 43 Henn V, Steinbach S, Büchner K, Presek P, Kroczek RA. The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40. Blood 2001; 98 (04) 1047-1054
• 44 Burdon KP, Langefeld CD, Beck SR. et al. Variants of the CD40 gene but not of the CD40L gene are associated with coronary artery calcification in the Diabetes Heart Study (DHS). Am Heart J 2006; 151 (03) 706-711
• 45 Basalyga DM, Simionescu DT, Xiong W, Baxter BT, Starcher BC, Vyavahare NR. Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation 2004; 110 (22) 3480-3487
• 46 Qin X, Corriere MA, Matrisian LM, Guzman RJ. Matrix metalloproteinase inhibition attenuates aortic calcification. Arterioscler Thromb Vasc Biol 2006; 26 (07) 1510-1516
• 47 Shi G, Field DJ, Long X. et al. Platelet factor 4 mediates vascular smooth muscle cell injury responses. Blood 2013; 121 (21) 4417-4427
• 48 Yoshida T, Kaestner KH, Owens GK. Conditional deletion of Krüppel-like factor 4 delays downregulation of smooth muscle cell differentiation markers but accelerates neointimal formation following vascular injury. Circ Res 2008; 102 (12) 1548-1557
• 49 Pitsilos S, Hunt J, Mohler ER. et al. Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters. Thromb Haemost 2003; 90 (06) 1112-1120
• 50 Sachais BS, Turrentine T, Dawicki McKenna JM, Rux AH, Rader D, Kowalska MA. Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE-/- mice. Thromb Haemost 2007; 98 (05) 1108-1113
• 51 Kaczor DM, Kramann R, Hackeng TM, Schurgers LJ, Koenen RR. Differential effects of platelet factor 4 (CXCL4) and its non-allelic variant (CXCL4L1) on cultured human vascular smooth muscle cells. Int J Mol Sci 2022; 23 (02) 580
• 52 Dhore CR, Cleutjens JP, Lutgens E. et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21 (12) 1998-2003
• 53 Bini A, Mann KG, Kudryk BJ, Schoen FJ. Noncollagenous bone matrix proteins, calcification, and thrombosis in carotid artery atherosclerosis. Arterioscler Thromb Vasc Biol 1999; 19 (08) 1852-1861
• 54 Kristjansdottir HL, Mellström D, Johansson P. et al. High platelet count is associated with low bone mineral density: the MrOS Sweden cohort. Osteoporos Int 2021; 32 (05) 865-871
• 55 Kim J, Kim HS, Lee HS, Kwon YJ. The relationship between platelet count and bone mineral density: results from two independent population-based studies. Arch Osteoporos 2020; 15 (01) 43
• 56 Gössl M, Mödder UI, Atkinson EJ, Lerman A, Khosla S. Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis. J Am Coll Cardiol 2008; 52 (16) 1314-1325
• 57 Foresta C, De Toni L, Biagioli A, Ganz F, Magagna S, Caretta N. Increased levels of osteocalcin-positive endothelial progenitor cells in patients affected by erectile dysfunction and cavernous atherosclerosis. J Sex Med 2010; 7 (2 Pt 1): 751-757
• 58 Fadini GP, Albiero M, Menegazzo L. et al. Widespread increase in myeloid calcifying cells contributes to ectopic vascular calcification in type 2 diabetes. Circ Res 2011; 108 (09) 1112-1121
• 59 McCarthy HS, Williams JH, Davie MW, Marshall MJ. Platelet-derived growth factor stimulates osteoprotegerin production in osteoblastic cells. J Cell Physiol 2009; 218 (02) 350-354
• 60 Schinke T, Karsenty G. Vascular calcification–a passive process in need of inhibitors. Nephrol Dial Transplant 2000; 15 (09) 1272-1274
• 61 Kautbally S, Lepropre S, Onselaer MB. et al. Platelet acetyl-CoA carboxylase phosphorylation: a risk stratification marker that reveals platelet-lipid interplay in coronary artery disease patients. JACC Basic Transl Sci 2019; 4 (05) 596-610
• 62 Salabei JK, Cummins TD, Singh M, Jones SP, Bhatnagar A, Hill BG. PDGF-mediated autophagy regulates vascular smooth muscle cell phenotype and resistance to oxidative stress. Biochem J 2013; 451 (03) 375-388
• 63 Betsholtz C, Keller A. PDGF, pericytes and the pathogenesis of idiopathic basal ganglia calcification (IBGC). Brain Pathol 2014; 24 (04) 387-395
• 64 Morisaki N, Takahashi K, Shiina R. et al. Platelet-derived growth factor is a potent stimulator of expression of intercellular adhesion molecule-1 in human arterial smooth muscle cells. Biochem Biophys Res Commun 1994; 200 (01) 612-618
• 65 Liu J, Ma KL, Gao M. et al. Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients. PLoS One 2012; 7 (10) e47217
• 66 Liu B, Poon M, Taubman MB. PDGF-BB enhances monocyte chemoattractant protein-1 mRNA stability in smooth muscle cells by downregulating ribonuclease activity. J Mol Cell Cardiol 2006; 41 (01) 160-169
• 67 Chen KC, Zhou Y, Xing K, Krysan K, Lou MF. Platelet derived growth factor (PDGF)-induced reactive oxygen species in the lens epithelial cells: the redox signaling. Exp Eye Res 2004; 78 (06) 1057-1067
• 68 Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 2001; 31 (04) 509-519
• 69 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 Biol Chem 2008; 283 (22) 15319-15327
• 70 Balderman JA, Lee HY, Mahoney CE. et al. Bone morphogenetic protein-2 decreases microRNA-30b and microRNA-30c to promote vascular smooth muscle cell calcification. J Am Heart Assoc 2012; 1 (06) e003905
• 71 Nakagawa Y, Ikeda K, Akakabe Y. et al. Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo. Arterioscler Thromb Vasc Biol 2010; 30 (10) 1908-1915
• 72 Novak S, Madunic J, Shum L. et al. PDGF inhibits BMP2-induced bone healing. NPJ Regen Med 2023; 8 (01) 3
• 73 Derwall M, Malhotra R, Lai CS. et al. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32 (03) 613-622
• 74 Mendonça MC, Koles N, Doi SQ, Sellitti DF. Transforming growth factor-beta1 regulation of C-type natriuretic peptide expression in human vascular smooth muscle cells: dependence on TSC22D1. Am J Physiol Heart Circ Physiol 2010; 299 (06) H2018-H2027
• 75 Huang Z, Li J, Jiang Z, Qi Y, Tang C, Du J. Effects of adrenomedullin, C-type natriuretic peptide, and parathyroid hormone-related peptide on calcification in cultured rat vascular smooth muscle cells. J Cardiovasc Pharmacol 2003; 42 (01) 89-97
• 76 Ponte AL, Marais E, Gallay N. et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 2007; 25 (07) 1737-1745
• 77 Collett GD, Sage AP, Kirton JP, Alexander MY, Gilmore AP, Canfield AE. Axl/phosphatidylinositol 3-kinase signaling inhibits mineral deposition by vascular smooth muscle cells. Circ Res 2007; 100 (04) 502-509
• 78 Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation?. Curr Pharm Des 2011; 17 (01) 47-58
• 79 Jagroop IA, Clatworthy I, Lewin J, Mikhailidis DP. Shape change in human platelets: measurement with a channelyzer and visualisation by electron microscopy. Platelets 2000; 11 (01) 28-32
• 80 Jung DH, Lee HR, Lee YJ, Kim JK, Park BJ, Shim JY. The association between coronary artery calcification and mean platelet volume in the general population. Platelets 2011; 22 (08) 567-571
• 81 Vagdatli E, Gounari E, Lazaridou E, Katsibourlia E, Tsikopoulou F, Labrianou I. Platelet distribution width: a simple, practical and specific marker of activation of coagulation. Hippokratia 2010; 14 (01) 28-32
• 82 He S, Lei W, Li J. et al. Relation of platelet parameters with incident cardiovascular disease (the Dongfeng-Tongji cohort study). Am J Cardiol 2019; 123 (02) 239-248
• 83 Tafelmeier M, Fischer A, Orsó E. et al. Mildly oxidized HDL decrease agonist-induced platelet aggregation and release of pro-coagulant platelet extracellular vesicles. J Steroid Biochem Mol Biol 2017; 169: 176-188
• 84 Murphy AJ, Bijl N, Yvan-Charvet L. et al. Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nat Med 2013; 19 (05) 586-594
• 85 Vergeer M, Korporaal SJ, Franssen R. et al. Genetic variant of the scavenger receptor BI in humans. N Engl J Med 2011; 364 (02) 136-145
• 86 Qiu YJ, Luo JY, Luo F. et al. Prognostic value of the PDW/HDL-C ratio in patients with chest pain symptoms and coronary artery calcification. Front Cardiovasc Med 2022; 9: 824955