Skip to main content
SpringerLink
Log in

Cardiac and Vascular Receptors and Signal Transduction

  • Chapter
  • First Online:
Handbook of Cardiac Anatomy, Physiology, and Devices

Abstract

Cellular physiological functions are regulated via signaling mechanisms in essentially any cell type of any organ. While myocardial cells are unique in that they are interconnected to each other via gap junctions and thus act as an electrical syncytium, there is nevertheless an enormous number of important cellular receptors that allow individual cells to receive and respond to various signals. Inflammation plays a very important role in cardiovascular disease. For example, device-based interventions such as coronary stenting may activate inflammation via a series of complex signaling processes. Importantly, inflammation pathways also play a central role in the elicitation of atherosclerosis, myocardial infarction, and/or heart failure. It is the general aim of this chapter to review the role and signaling mechanisms of selected physiologically and pathophysiologically important cardiac and vascular receptors with emphasis on G-protein-coupled receptors (e.g., beta-adrenergic receptors), non-G-protein-coupled receptor systems, such as guanylyl cyclase-related receptors (e.g., receptors for nitric oxide), and finally, to discuss the importance and complexity of inflammation in the pathobiology of coronary artery disease and stenting.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmembrane-spanning receptors and heart function. Nature 2002;415:206–12.

    Article  PubMed  CAS  Google Scholar 

  2. del Monte F, Kaufmann AJ, Poole-Wilson PA, et al. Coexistence of functioning beta-1 and beta-2 adrenoreceptors in single myocytes from human ventricle. Circulation 1993;88:854–63.

    PubMed  Google Scholar 

  3. Bristow MR, Hershberger RE, Port JD, et al. Beta-adrenergic pathways in non-failing and failing human ventricular myocardium. Circulation 1990;82:112–25.

    Article  Google Scholar 

  4. Opie L. Receptors and signal transduction. In:Opie L, ed. The heart: Physiology, from cell to circulation. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1998:173–207.

    Google Scholar 

  5. Hohl CM, Li Q. Compartmentation of camp in adult canine ventricular myocytes. Relation to single cell free calcium transients. Circ Res 1991;69:1369–79.

    PubMed  CAS  Google Scholar 

  6. Lader AS, Xiao YF, Ishikawa Y, et al. Cardiac gsalpha overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway. Proc Natl Acad Sci USA 1998;95:9669–74.

    Article  PubMed  CAS  Google Scholar 

  7. Port JD, Bristow MR. Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure. J Mol Cell Cardiol 2001;33:887–905.

    Article  PubMed  CAS  Google Scholar 

  8. Gauthier C, Langin D, Balligand JL. Beta3-adrenoceptors in the cardiovascular system. Trends Pharmacol Sci 2000;21:426–31.

    Article  PubMed  CAS  Google Scholar 

  9. Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG. The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta-2 adrenergic recedptor into clathrin coated pits. J Biol Chem 2000;275:23120–6.

    Article  PubMed  CAS  Google Scholar 

  10. Luttrell LM, Ferguson SS, Daakay Y, et al. Beta-arrestin-dependent formation of beta-2 adrenergic receptor-Src protein kinase complexes. Science 1999;283:655–61.

    Article  PubMed  CAS  Google Scholar 

  11. Shenoy SK, McDonald PH, Kohout TA, Lefkowitz RJ. Regulation of receptor fate by ubiquitination of activated beta-2 adrenergic receptor and beta-arrestin. Science 2001;294:1574–77.

    Article  Google Scholar 

  12. Mann D, Kent R, Parsons B, Cooper IVG. Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation 1992;85:790–804.

    PubMed  CAS  Google Scholar 

  13. Bristow MR, Ginsburg R, Umans V, et al. Beta 1 and beta 2-adrenergic receptor subpopulations in nonfailing and failing human ventricular myocardium: Coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res 1986;59:297–309.

    PubMed  CAS  Google Scholar 

  14. Ungerer M, Parruti G, Böhn M, et al. Expression of beta-arrestins and beta-adrnergic receptor kinases in the failing human heart. Circ Res 1994;74:206–13.

    PubMed  CAS  Google Scholar 

  15. Steinberg SF. The molecular basis for distinct beta-AR subtype action in cardiomyocytes. Circ Res 1999;85:1101–11.

    PubMed  CAS  Google Scholar 

  16. Lader AS, Xiao YF, Ishikawa Y, et al. Cardiac gsalpha overexpression enhances L-type calcium channels through an adenylyl cyclase independent pathway. Proc Natl Acad Sci USA 1998;95:9669–74.

    Article  PubMed  CAS  Google Scholar 

  17. Communal C, Singh K, Sawyer DB, Colucci WS. Opposing effects of beta-1 and beta-2 adrenergic receptor on cardiac myocyte apoptosis: Role of a pertussis toxin sensitive G protein. Circulation 1999;100:2210–2.

    PubMed  CAS  Google Scholar 

  18. Zaugg M, Xu W, Lucchinetti E, Shafiq SA, Jamali NZ, Siddiqui MA. Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation 2000;102:344–50.

    PubMed  CAS  Google Scholar 

  19. Bisognano JD, Weinberger HD, Bohlmeyer TJ, et al. Myocardial-directed overexpression of the human beta-1-adrenergic receptor in transgenic mice. J Mol Cell Cardiol 2000;32:817–30.

    Article  PubMed  CAS  Google Scholar 

  20. Saito S, Hiroi Y, Zou Y, et al. Beta-adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes. J Biol Chem 2000;275:34528–33.

    Article  PubMed  CAS  Google Scholar 

  21. Lowes BD, Gill EA, Abraham WT, et al. Effects of carvedilol on left ventricular mass, chamber geometry, and mitral regurgitation in chronic heart failure. Am J Cardiol 1999;83:1201–5.

    Article  PubMed  CAS  Google Scholar 

  22. Liggett SB, Wagoner LE, Craft LL, et al. The Ile164 Beta-2 AR polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998;102:1534–9.

    Article  PubMed  CAS  Google Scholar 

  23. Wagoner LE, Craft LL, Singh B, et al. Polymorphisms of the beta-2 AR determine exercise capacity in patients with heart failure. Circ Res 2000;86:834–40.

    PubMed  CAS  Google Scholar 

  24. Graham RM, Perez DM, Hwa J, Piascik MT. Alpha-AR subtypes. Molecular structure, function and signaling. Circ Res 1996;78:737–49.

    PubMed  CAS  Google Scholar 

  25. Otani H, Otani H, Das DK. Alpha-1 adrenoreceptor mediated phosphoinisotidie breakdown and inotropic response in rate left ventricular papillary muscles. Circ Res 1988;62:8–17.

    PubMed  CAS  Google Scholar 

  26. Hwang KC, Grady CD, Sweet WE, Moravec CS. Alpha-1 adrenergic receptor coupling with Gh in the failing human heart. Circulation 1996;94:718–26.

    PubMed  CAS  Google Scholar 

  27. Choi DJ, Koch WJ, Hunter JJ, Rockman HA. Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-ARK. J Biol Chem 1997;272:17223–9.

    Article  PubMed  CAS  Google Scholar 

  28. Knowlton KU, Michael MC, Itani, et al. The alpha1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy. J Biol Chem 1993;268:15374–80.

    Google Scholar 

  29. Sugden PH. Signaling in myocardial hypertrophy: Life after calcineurin? Circ Res 1999;84:633–46.

    PubMed  CAS  Google Scholar 

  30. Barki-Harrington L, Luttrell LM, Rockman HA. Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist. Circulation 2003;108:1611–8.

    Article  PubMed  CAS  Google Scholar 

  31. Dzimiri N. Receptor crosstalk: Implications for cardiovascular function, disease and therapy. Eur J Biochem 2002;269:4713–30.

    Article  PubMed  CAS  Google Scholar 

  32. Münzel T, Feil R, Mülsch A, Lohmann SM, Hofmann F, Walter U. Physiology and pathophysiology of vascular signaling controlled by cyclic guanosine 3',5'-cyclic monophosphate-dependent protein kinase. Circulation 2003;108:2172–83.

    Article  PubMed  Google Scholar 

  33. von der Leyen HE, Dzau VJ. Therapeutic potential of nitric oxide synthase gene manipulation. Circulation 2001;103:2760–5.

    PubMed  Google Scholar 

  34. Loscalzo J. Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res 2001;88:756–62.

    Article  PubMed  CAS  Google Scholar 

  35. Champion HC, Skaf MW, Hare JM. Role of nitric oxide in the pathophysiology of heart failure. Heart Fail Rev 2003;8:35–46.

    Article  PubMed  CAS  Google Scholar 

  36. Jugdutt BI. Nitric oxide and cardiovascular protection. Heart Fail Rev 2003;8:29–34.

    Article  PubMed  CAS  Google Scholar 

  37. Young-Myeong K, Bombeck CA, Billiar TR. Nitric oxide as a bifunctional regulator of apoptosis. Circ Res 1999;84:253–6.

    Google Scholar 

  38. Kuhn M. Structure, regulation, and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase A. Circ Res 2003;93:700–9.

    Article  PubMed  CAS  Google Scholar 

  39. Nobuyoshi M, Kimura T, Nosaka H, et al. Restenosis after successful percutaneous transluminal coronary angioplasty: Serial angiographic follow-up of 229 patients. J Am Coll Cardiol 1988;12:616–23.

    PubMed  CAS  Google Scholar 

  40. Kipshidze NN, Tsapenko ML, Leon MB, Stone GW, Moses JW. Update on drug-eluting coronary stents. Expert Rev Cardiovasc Ther 2005;3:953–68.

    Article  PubMed  CAS  Google Scholar 

  41. van den Brand MJ, Rensing BJ, Morel MA, et al. The effect of completeness of revascularization on event-free survival at one year in the ARTS trial. J Am Coll Cardiol 2002;39:559–64.

    Article  PubMed  Google Scholar 

  42. Topol EJ, Serruys PW. Frontiers in interventional cardiology. Circulation 1998;98:1802–20.

    PubMed  CAS  Google Scholar 

  43. Serruys PW, Foley DP, Suttorp MJ. A randomized comparison of the value of additional stenting after optimal balloon angioplasty for long coronary lesions: Final results of the additional value of NIR stents for treatment of long coronary lesions (ADVANCE) study. J Am Coll Cardiol 2002;39:393–9.

    Article  PubMed  Google Scholar 

  44. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 1994;331:496–501.

    Article  PubMed  CAS  Google Scholar 

  45. Scott NA. Restenosis following implantation of bare metal coronary stents: Pathophysiology and pathways involved in the vascular response to injury. Adv Drug Deliv Rev 2006;58:358–76.

    Article  PubMed  CAS  Google Scholar 

  46. Faries PL, Rohan DI, Takahara H. Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration. J Vasc Surg 2001;33:601–7.

    Article  PubMed  CAS  Google Scholar 

  47. El-Omar MM, Dangas G, Iakovou I, Mehran R. Update on in-stent restenosis. Curr Interv Cardiol Rep 2001;3:296–305.

    PubMed  Google Scholar 

  48. Hill RA, Boland A, Dickson R, et al. Drug-eluting stents: A systematic review and economic evaluation. Health Technol Assess 2007;11:iii, xi-221.

    Google Scholar 

  49. Htay T, Liu MW. Drug-eluting stent: A review and update. Vasc Health Risk Manag 2005;1:263–76.

    Article  PubMed  CAS  Google Scholar 

  50. Steffel J, Tanner FC. Biological effects of drug-eluting stents in the coronary circulation. Herz 2007;32:268–73.

    Article  PubMed  Google Scholar 

  51. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451:914–8.

    Google Scholar 

  52. Kaul S, Shah PK, Diamond GA. As time goes by: Current status and future directions in the controversy over stenting. J Am Coll Cardiol 2007;50:128–37.

    Article  PubMed  Google Scholar 

  53. Bavry AA, Kumbhani DJ, Helton TJ, Bhatt DL. Risk of thrombosis with the use of sirolimus-eluting stents for percutaneous coronary intervention (from registry and clinical trial data). Am J Cardiol 2005;95:1469–72.

    Article  PubMed  CAS  Google Scholar 

  54. Moreno R, Fernández C, Hernández R, et al. Drug-eluting stent thrombosis: Results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 2005;45:954–9.

    Article  PubMed  CAS  Google Scholar 

  55. Luscher TF, Steffel J, Eberli FR, et al. Drug-eluting stent and coronary thrombosis: Biological mechanisms and clinical implications. Circulation 2007;115:1051–8.

    Article  PubMed  Google Scholar 

  56. Legrand V. Therapy insight: Diabetes and drug-eluting stents. Nat Clin Pract Cardiovasc Med 2007;4:143–50.

    Article  PubMed  CAS  Google Scholar 

  57. Kawaguchi R, Angiolillo DJ, Futamatsu H, Suzuki N, Bass TA, Costa MA. Stent thrombosis in the era of drug-eluting stents. Minerva Cardioangiol 2007;55:199–211.

    PubMed  CAS  Google Scholar 

  58. Forrester JS, Fishbein M, Helfant R, Fagin J. A paradigm for restenosis based on cell biology: Clues for the development of new preventive therapies. J Am Coll Cardiol 1991;17:758–69.

    Article  PubMed  CAS  Google Scholar 

  59. Costa MA, Simon DI. Molecular basis of restenosis and drug-eluting stents. Circulation 2005;111:2257–73.

    Article  PubMed  Google Scholar 

  60. Libby P. Atherosclerosis: Disease biology affecting the coronary vasculature. Am J Cardiol 2006;98:3–9Q.

    Article  CAS  Google Scholar 

  61. Casscells W, Engler D, Willerson JT. Mechanisms of restenosis. Tex Heart Inst J 1994;21:68–77.

    PubMed  CAS  Google Scholar 

  62. Welt FG, Rogers C. Inflammation and restenosis in the stent era. Arterioscler Thromb Vasc Biol 2002;22:1769–76.

    Article  PubMed  CAS  Google Scholar 

  63. Mintz GS, Popma JJ, Hong MK, et al. Intravascular ultrasound findings after excimer laser coronary angioplasty. Cathet Cardiovasc Diagn 1996;37:113–8.

    Article  PubMed  CAS  Google Scholar 

  64. Lundmark K, Tran PK, Kinsella MG, Clowes AW, Wight TN, Hedin U. Perlecan inhibits SMC adhesion to fibronectin: Role of heparan sulfate. J Cell Physiol 2001;188:67–74.

    Article  PubMed  CAS  Google Scholar 

  65. Lerman A. Restenosis: Another “dysfunction” of the endothelium. Circulation 2005;111:8–10.

    Article  PubMed  Google Scholar 

  66. Muto A, Fitzgerald TN, Pimiento JM, et al. Smooth muscle cell signal transduction: Implications of vascular biology for vascular surgeons. J Vasc Surg 2007;45:A15–24.

    Article  PubMed  Google Scholar 

  67. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004;84:767–801.

    Article  PubMed  CAS  Google Scholar 

  68. Li X, et al. Suppression of smooth-muscle alpha-actin expression by platelet-derived growth factor in vascular smooth-muscle cells involves Ras and cytosolic phospholipase A2. Biochem J 1997;327:709–16.

    PubMed  Google Scholar 

  69. Zalewski A, Shi Y, Johnson AG. Diverse origin of intimal cells: Smooth muscle cells, myofibroblasts, fibroblasts, and beyond? Circ Res 2002;91:652–5.

    Article  PubMed  CAS  Google Scholar 

  70. Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI, West AB. Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 1999;277:C1–9.

    PubMed  CAS  Google Scholar 

  71. Yokote K, Take A, Nakaseko C, et al. Bone marrow-derived vascular cells in response to injury. J Atheroscler Thromb 2003;10:205–10.

    Article  PubMed  Google Scholar 

  72. Bornfeldt KE, Krebs EG. Crosstalk between protein kinase A and growth factor receptor signaling pathways in arterial smooth muscle. Cell Signal 1999;11:465–77.

    Article  PubMed  CAS  Google Scholar 

  73. Seger R, Krebs EG. The MAPK signaling cascade. Faseb J 1995;9:726–35.

    PubMed  CAS  Google Scholar 

  74. Asada H. Paszkowiak J, Teso D, et al. Sustained orbital shear stress stimulates smooth muscle cell proliferation via the extracellular signal-regulated protein kinase 1/2 pathway. J Vasc Surg 2005;42:772–80.

    Article  PubMed  Google Scholar 

  75. Nishida E, Gotoh Y. The MAP kinase cascade is essential for diverse signal transduction pathways. Trends Biochem Sci 1993;18:128–31.

    Article  PubMed  CAS  Google Scholar 

  76. Marshall CJ. Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell 1995;80:179–85.

    Article  PubMed  CAS  Google Scholar 

  77. Liu Y, McDonald OG, Shang Y, Hoofnagle MH, Owens GK. Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression. J Biol Chem 2005;280:9719–27.

    Article  PubMed  CAS  Google Scholar 

  78. McDonald OG, Warnhoff BR, Hoofnagle MH, Owens GK. Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo. J Clin Invest 2006;116:36–48.

    Article  PubMed  CAS  Google Scholar 

  79. Hedin U, Roy J, Tran PK. Control of smooth muscle cell proliferation in vascular disease. Curr Opin Lipidol 2004;15:559–65.

    Article  PubMed  CAS  Google Scholar 

  80. Geng YJ, Libby P. Progression of atheroma: A struggle between death and procreation. Arterioscler Thromb Vasc Biol 2002;22:1370–80.

    Article  PubMed  CAS  Google Scholar 

  81. Raines EW. The extracellular matrix can regulate vascular cell migration, proliferation, and survival: Relationships to vascular disease. Int J Exp Pathol 2000;81:173–82.

    Article  PubMed  CAS  Google Scholar 

  82. Dzau VJ, Braun-Dullaeus RC, Sedding DG. Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies. Nat Med 2002;8:1249–56.

    Article  PubMed  CAS  Google Scholar 

  83. Walworth NC. Cell-cycle checkpoint kinases: Checking in on the cell cycle. Curr Opin Cell Biol 2000;12:697–704.

    Article  PubMed  CAS  Google Scholar 

  84. Weinberg RA. E2F and cell proliferation: A world turned upside down. Cell 1996;85:457–9.

    Article  PubMed  CAS  Google Scholar 

  85. Harbour JW, Dean DC. Rb function in cell-cycle regulation and apoptosis. Nat Cell Biol 2000;2:E65–7.

    Article  PubMed  CAS  Google Scholar 

  86. Tanner FC, Boehm M, Akyürek LM, et al. Differential effects of the cyclin-dependent kinase inhibitors p27(Kip1), p21(Cip1), and p16(Ink4) on vascular smooth muscle cell proliferation. Circulation 2000;101:2022–5.

    PubMed  CAS  Google Scholar 

  87. Gizard F, Bruemmer D. Transcriptional control of vascular smooth muscle cell proliferation by peroxisome proliferator-activated receptor-gamma: Therapeutic implications for cardiovascular diseases. PPAR Res 2008;2008:429123.

    Article  PubMed  CAS  Google Scholar 

  88. Sherr CJ, Roberts JM. CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev 1999;13:1501–12.

    Article  PubMed  CAS  Google Scholar 

  89. Braun-Dullaeus RC, Mann MJ, Dzau VJ. Cell cycle progression: New therapeutic target for vascular proliferative disease. Circulation 1998;98:82–9.

    PubMed  CAS  Google Scholar 

  90. Quizhpe AR, Feres F, de Ribamar Costa J Jr., et al. Drug-eluting stents vs bare metal stents for the treatment of large coronary vessels. Am Heart J 2007;154:373–8.

    Article  PubMed  CAS  Google Scholar 

  91. Neuhaus P, Klupp J, Langrehr JM. mTOR inhibitors: An overview. Liver Transpl 2001;7:473–84.

    Article  PubMed  CAS  Google Scholar 

  92. Sehgal SN. Sirolimus: Its discovery, biological properties, and mechanism of action. Transplant Proc 2003;35:7–14S.

    Article  CAS  Google Scholar 

  93. Ruygrok PN, Muller DW, Serruys PW. Rapamycin in cardiovascular medicine. Intern Med J 2003;33:103–9.

    Article  PubMed  CAS  Google Scholar 

  94. Abizaid A. Sirolimus-eluting coronary stents: A review. Vasc Health Risk Manag 2007;3:191–201.

    Article  PubMed  CAS  Google Scholar 

  95. Larkin JM, Kaye SB. Epothilones in the treatment of cancer. Expert Opin Investig Drugs 2006;15:691–702.

    Article  PubMed  CAS  Google Scholar 

  96. Sheiban I, Moretti C, Oliaro E, et al. Evolving standard in the treatment of coronary artery disease. Drug-eluting stents. Minerva Cardioangiol 2003;51:485–92.

    PubMed  CAS  Google Scholar 

  97. Kukreja N, Onuma Y, Daemen J, Serruys PW. The future of drug-eluting stents. Pharmacol Res 2008;57:171–80.

    Article  PubMed  CAS  Google Scholar 

  98. Okamoto S, Inden M, Setsuda M, Konishi T, Nakano T. Effects of trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1992;123:1439–44.

    Article  PubMed  CAS  Google Scholar 

  99. Powell JS, Clozel JP, Müller RK, et al. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science 1989;245:186–8.

    Article  PubMed  CAS  Google Scholar 

  100. Garas SM, Huber P, Scott NA. Overview of therapies for prevention of restenosis after coronary interventions. Pharmacol Ther 2001;92:165–78.

    Article  PubMed  CAS  Google Scholar 

  101. Reidy MA, Fingerle J, Lindner V. Factors controlling the development of arterial lesions after injury. Circulation 1992;86:III43–6.

    PubMed  CAS  Google Scholar 

  102. Meredith IT, Anderson TJ, Uehata A, Yeung AC, Selwyn AP, Ganz P. Role of endothelium in ischemic coronary syndromes. Am J Cardiol 1993;72:27–31C; discussion 31–32C.

    Article  Google Scholar 

  103. Versari D, Lerman LO, Lerman A. The importance of reendothelialization after arterial injury. Curr Pharm Des 2007;13:1811–24.

    Article  PubMed  CAS  Google Scholar 

  104. Rao RM, Yang L, Garcia-Cardena G, Luscinskas FW. Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circ Res 2007;101:234–47.

    Article  PubMed  CAS  Google Scholar 

  105. Berk BC. Vascular smooth muscle growth: Autocrine growth mechanisms. Physiol Rev 2001;81:999–1030.

    PubMed  CAS  Google Scholar 

  106. Langille BL, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 1986;231:405–7.

    Article  PubMed  CAS  Google Scholar 

  107. Datta YH, Ewenstein BM. Regulated secretion in endothelial cells: Biology and clinical implications. Thromb Haemost 2001;86:1148–55.

    PubMed  CAS  Google Scholar 

  108. Celermajer DS. Endothelial dysfunction: Does it matter? Is it reversible? J Am Coll Cardiol 1997;30:325–33.

    Article  PubMed  CAS  Google Scholar 

  109. Leopold JA, Loscalzo J. Clinical importance of understanding vascular biology. Cardiol Rev 2000;8:115–23.

    Article  PubMed  CAS  Google Scholar 

  110. Tanguay JF. Vascular healing after stenting: The role of 17-beta-estradiol in improving re-endothelialization and reducing restenosis. Can J Cardiol 2005;21:1025–30.

    PubMed  CAS  Google Scholar 

  111. Adams B. Xiao Q, Xu Q. Stem cell therapy for vascular disease. Trends Cardiovasc Med 2007;17:246–51.

    Article  PubMed  CAS  Google Scholar 

  112. Sprague EA, Luo J, Palmaz JC. Endothelial cell migration onto metal stent surfaces under static and flow conditions. J Long Term Eff Med Implants 2000;10:97–110.

    PubMed  CAS  Google Scholar 

  113. Davies PF. Flow-mediated endothelial mechanotransduction. Physiol Rev 1995;75:519–60.

    PubMed  CAS  Google Scholar 

  114. Garcia-Cardena G, Comander J, Anderson KR, Blackman BR, Gimbrone MA Jr. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proc Natl Acad Sci USA 2001;98:4478–85.

    Article  PubMed  CAS  Google Scholar 

  115. Lin K, Hsu PP, Chen BP, et al. Molecular mechanism of endothelial growth arrest by laminar shear stress. Proc Natl Acad Sci USA 2000;97:9385–9.

    Article  PubMed  CAS  Google Scholar 

  116. Levesque MJ, Nerem RM, Sprague EA. Vascular endothelial cell proliferation in culture and the influence of flow. Biomaterials 1990;11:702–7.

    Article  PubMed  CAS  Google Scholar 

  117. LaDisa JF Jr., Guler I, Olson LE, et al. Three-dimensional computational fluid dynamics modeling of alterations in coronary wall shear stress produced by stent implantation. Ann Biomed Eng 2003;31:972–80.

    Article  PubMed  Google Scholar 

  118. Colombo A, Sangiorgi G. The monocyte: The key in the lock to reduce stent hyperplasia? J Am Coll Cardiol 2004;43:24–6.

    Article  PubMed  Google Scholar 

  119. Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999;99:44–52.

    PubMed  CAS  Google Scholar 

  120. Welt FG, Tso C. Edellman ER, et al., Leukocyte recruitment and expression of chemokines following different forms of vascular injury. Vasc Med 2003;8:1–7.

    Article  PubMed  Google Scholar 

  121. Tanaka H, Sukhova GK, Swnason SJ, et al. Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury. Circulation 1993;88:1788–803.

    PubMed  CAS  Google Scholar 

  122. Rogers C, Welt FG, Karnovsky MJ, Edelman ER. Monocyte recruitment and neointimal hyperplasia in rabbits. Coupled inhibitory effects of heparin. Arterioscler Thromb Vasc Biol 1996;16:1312–8.

    Article  PubMed  CAS  Google Scholar 

  123. Rogers C, Edelman ER, Simon DI. A mAb to the beta2-leukocyte integrin Mac-1 (CD11b/CD18) reduces intimal thickening after angioplasty or stent implantation in rabbits. Proc Natl Acad Sci USA 1998;95:10134–9.

    Article  PubMed  CAS  Google Scholar 

  124. McEver RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest 1997;100:S97–103.

    Article  PubMed  CAS  Google Scholar 

  125. Weber C. Platelets and chemokines in atherosclerosis: Partners in crime. Circ Res 2005;96:612–6.

    Article  PubMed  CAS  Google Scholar 

  126. Kitamoto S, Egashira K. Anti-monocyte chemoattractant protein-1 gene therapy for cardiovascular diseases. Expert Rev Cardiovasc Ther 2003;1:393–400.

    Article  PubMed  CAS  Google Scholar 

  127. Wainwright CL, Miller AM, Wadsworth RM. Inflammation as a key event in the development of neointima following vascular balloon injury. Clin Exp Pharmacol Physiol 2001;28:891–5.

    Article  PubMed  CAS  Google Scholar 

  128. Cipollone F, Marini M, Fazia M. Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty. Arterioscler Thromb Vasc Biol 2001;21:327–34.

    Article  PubMed  CAS  Google Scholar 

  129. Oshima S, Ogawa H, Hokimoto S, et al., Plasma monocyte chemoattractant protein-1 antigen levels and the risk of restenosis after coronary stent implantation. Jpn Circ J 2001;65:261–4.

    Article  PubMed  CAS  Google Scholar 

  130. Bursill CA, Channon KM, Greaves DR. The role of chemokines in atherosclerosis: Recent evidence from experimental models and population genetics. Curr Opin Lipidol 2004;15:145–9.

    Article  PubMed  CAS  Google Scholar 

  131. Tashiro H, Shimokawa H, Sadamatsu K, Aoki T, Yamamoto K. Role of cytokines in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty. Coron Artery Dis 2001;12:107–13.

    Article  PubMed  CAS  Google Scholar 

  132. Arend WP, Guthridge CJ. Biological role of interleukin 1 receptor antagonist isoforms. Ann Rheum Dis 2000;59:i60–4.

    Article  PubMed  CAS  Google Scholar 

  133. Sardella G, Mariani P, D’Alessandro M, et al. Early elevation of interleukin-1beta and interleukin-6 levels after bare or drug-eluting stent implantation in patients with stable angina. Thromb Res 2006;117:659–64.

    Article  PubMed  CAS  Google Scholar 

  134. Odrowaz-Sypniewska G. Markers of pro-inflammatory and pro-thrombotic state in the diagnosis of metabolic syndrome. Adv Med Sci 2007;52:246–50.

    PubMed  CAS  Google Scholar 

  135. Monraats PS, Pires NM, Schepers A, et al. Tumor necrosis factor-alpha plays an important role in restenosis development. Faseb J 2005;19:1998–2004.

    Article  PubMed  CAS  Google Scholar 

  136. Kawamoto R, Hatakeyama K, Imamura T, et al. Relation of C-reactive protein to restenosis after coronary stent implantation and to restenosis after coronary atherectomy. Am J Cardiol 2004;94:104–7.

    Article  PubMed  CAS  Google Scholar 

  137. Mazer SP, Rabbani LE. Evidence for C-reactive protein’s role in (CRP) vascular disease: Atherothrombosis, immuno-regulation and CRP. J Thromb Thrombolysis 2004;17:95–105.

    Article  PubMed  CAS  Google Scholar 

  138. Gaspardone A, Versaci F, Tomai F, et al. C-Reactive protein, clinical outcome, and restenosis rates after implantation of different drug-eluting stents. Am J Cardiol 2006;97:1311–6.

    Article  PubMed  CAS  Google Scholar 

  139. Moreno PR, Bernardi VH, López-Cuéllar J, et al. Macrophage infiltration predicts restenosis after coronary intervention in patients with unstable angina. Circulation 1996;94:3098–102.

    PubMed  CAS  Google Scholar 

  140. Stakos DA, Kotsianidis I, Tziakas DN, et al. Leukocyte activation after coronary stenting in patients during the subacute phase of a previous ST-elevation myocardial infarction. Coron Artery Dis 2007;18:105–10.

    Article  PubMed  Google Scholar 

  141. Funayama H, Ishikawa SE, Kubo N, Yasu T, Saito M, Kawakami M. Close association of regional interleukin-6 levels in the infarct-related culprit coronary artery with restenosis in acute myocardial infarction. Circ J 2006;70:426–9.

    Article  PubMed  CAS  Google Scholar 

  142. Cipollone F, Ferri C, Desideri G, et al. Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty. Circulation 2003;108:2776–82.

    Article  PubMed  CAS  Google Scholar 

  143. Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol 2003;73:713–21.

    Article  PubMed  CAS  Google Scholar 

  144. Becker RC. Complicated myocardial infarction. Crit Pathw Cardiol 2003;2:125–52.

    PubMed  Google Scholar 

  145. Vishnevetsky D, Kiyanista VA, Gandhi PJ. CD40 ligand: A novel target in the fight against cardiovascular disease. Ann Pharmacother 2004;38:1500–8.

    Article  PubMed  CAS  Google Scholar 

  146. Yan JC, Ding S, Liang Y, et al. Relationship between upregulation of CD40 system and restenosis in patients after percutaneous coronary intervention. Acta Pharmacol Sin 2007;28:339–43.

    Article  PubMed  CAS  Google Scholar 

  147. Shebuski RJ, Kilgore KS. Role of inflammatory mediators in thrombogenesis. J Pharmacol Exp Ther 2002;300:729–35.

    Article  PubMed  CAS  Google Scholar 

  148. Giesen PL, Fyfe BS, Fallon JT, et al. Intimal tissue factor activity is released from the arterial wall after injury. Thromb Haemost 2000;83:622–8.

    PubMed  CAS  Google Scholar 

  149. Martorell L, Martinez-Gonzalez J, Rodriguez C, Gentile M, Calvayrac O, Badimon L. Thrombin and protease-activated receptors (PARs) in atherothrombosis. Thromb Haemost 2008;99;305–15.

    PubMed  Google Scholar 

  150. Hideshima T, Rodar K, Chauhan D, Anderson KC. Cytokines and signal transduction. Best Pract Res Clin Haematol 2005;18:509–24.

    Article  PubMed  CAS  Google Scholar 

  151. Barish GD, Atkins AR, Downes M, et al. PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc Natl Acad Sci USA 2008;105:4271–6.

    Article  PubMed  CAS  Google Scholar 

  152. Baron AD. Insulin resistance and vascular function. J Diabetes Complications 2002;16:92–102.

    Article  PubMed  Google Scholar 

  153. Kim F, Pham M, Luttrell I, et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res 2007;100:1589–96.

    Article  PubMed  CAS  Google Scholar 

  154. Nilsson J, Nilsson LM, Chen YM, Molkentin JD, Erlinge D, Gomez MF. High glucose activates nuclear factor of activated T cells in native vascular smooth muscle. Arterioscler Thromb Vasc Biol 2006;26:794–800.

    Article  PubMed  CAS  Google Scholar 

  155. Zhang L, Peppel K, Sivashanmugam P, et al. Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27:1087–94.

    PubMed  Google Scholar 

  156. Heyninck K, Beyaert R. Crosstalk between NF-kappaB-activating and apoptosis-inducing proteins of the TNF-receptor complex. Mol Cell Biol Res Commun 2001;4:259–65.

    Article  PubMed  CAS  Google Scholar 

  157. Schonbeck U, Libby P. CD40 signaling and plaque instability. Circ Res 2001;89:1092–103.

    Article  PubMed  CAS  Google Scholar 

  158. Vanichakarn P, Blair P, Wu C, Freedman JE, Chakrabarti S. Neutrophil CD40 enhances platelet-mediated inflammation. Thromb Res 2008;Feb 18 [Epub ahead of print].

    Google Scholar 

  159. Lutgens E, Lievens D, Beckers L, Donners M, Daemen M. CD40 and its ligand in atherosclerosis. Trends Cardiovasc Med 2007;17:118–23.

    Article  PubMed  CAS  Google Scholar 

  160. Chakrabarti S, Blair P, Freedman JE. CD40-40L signaling in vascular inflammation. J Biol Chem 2007;282:18307–17.

    Article  PubMed  CAS  Google Scholar 

  161. Zirlik A, Bavendiek U, Libby P, et al. TRAF-1, –2, –3, –5, and –6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells. Arterioscler Thromb Vasc Biol 2007;27:1101–7.

    Article  PubMed  CAS  Google Scholar 

  162. Hoge M, Amar S. Role of interleukin-1 in bacterial atherogenesis. Drugs Today (Barc) 2006;42:683–8.

    Article  CAS  Google Scholar 

  163. Fogal B, Hewett SJ. Interleukin-1beta: A bridge between inflammation and excitotoxicity? J Neurochem 2008;Mar 19 [Epub ahead of print].

    Google Scholar 

  164. Li X, Qin J. Modulation of Toll-interleukin 1 receptor mediated signaling. J Mol Med 2005;83:258–66.

    Article  PubMed  CAS  Google Scholar 

  165. Boraschi D, Tagliabue A. The interleukin-1 receptor family. Vitam Horm 2006;74:229–54.

    Article  PubMed  CAS  Google Scholar 

  166. Gottipati S, Rao NL, Fung-Leung WP. IRAK1: A critical signaling mediator of innate immunity. Cell Signal 2008;20:269–76.

    Article  PubMed  CAS  Google Scholar 

  167. Mullaly SC, Kubes P. Toll gates and traffic arteries: From endothelial TLR2 to atherosclerosis. Circ Res 2004;95:657–9.

    Article  PubMed  CAS  Google Scholar 

  168. Schoneveld AH, Oude Nijhuis MM, van Middelaar B, Laman JD, de Kleijn DP, Pasterkamp G. Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development. Cardiovasc Res 2005;66:162–9.

    Article  PubMed  CAS  Google Scholar 

  169. Shishido T, Nozaki N, Takahashi H, et al. Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injury. Biochem Biophys Res Commun 2006;345:1446–53.

    Article  PubMed  CAS  Google Scholar 

  170. Harrington LS, Belcher E, Moreno L, Carrier MJ, Mitchell JA. Homeostatic role of Toll-like receptor 4 in the endothelium and heart. J Cardiovasc Pharmacol Ther 2007;12:322–6.

    Article  PubMed  CAS  Google Scholar 

  171. de Kleijn MJ, Wilmink HW, Bots ML, et al. Hormone replacement therapy and endothelial function. Results of a randomized controlled trial in healthy postmenopausal women. Atherosclerosis 2001;159:357–65.

    Article  PubMed  Google Scholar 

  172. Martin MU, Wesche H. Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta 2002;1592:265–80.

    Article  PubMed  CAS  Google Scholar 

  173. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity. Annu Rev Immunol 2000;18:621–63.

    Article  PubMed  CAS  Google Scholar 

  174. Chen FE, Huang DB, Chen YQ, Ghosh G. Crystal structure of p50/p65 heterodimer of transcription factor NF-kappaB bound to DNA. Nature 1998;391:410–3.

    Article  PubMed  CAS  Google Scholar 

  175. Li ZW, Chu W, Hu Y, et al. The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis. J Exp Med 1999;189:1839–45.

    Article  PubMed  CAS  Google Scholar 

  176. Li X, Stark GR. NFkappaB-dependent signaling pathways. Exp Hematol 2002;30:285–96.

    Article  PubMed  CAS  Google Scholar 

  177. Bavry AA, Kumbhani DJ, Helton TJ, Borek PP, Mood GR, Bhatt DL. Late thrombosis of drug-eluting stents: A meta-analysis of randomized clinical trials. Am J Med 2006;119:1056–61.

    Article  PubMed  CAS  Google Scholar 

  178. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126–30.

    Article  PubMed  CAS  Google Scholar 

  179. Waters RE, Kandzari DE, Phillips HR, Crawford LE, Sketch MH Jr. Late thrombosis following treatment of in-stent restenosis with drug-eluting stents after discontinuation of antiplatelet therapy. Catheter Cardiovasc Interv 2005;65:520–4.

    Article  PubMed  Google Scholar 

  180. Eisenreich A, Celebi O, Goldin-Lang P, Schultheiss HP, Rauch U. Upregulation of tissue factor expression and thrombogenic activity in human aortic smooth muscle cells by irradiation, rapamycin and paclitaxel. Int Immunopharmacol 2008;8:307–11.

    Article  PubMed  CAS  Google Scholar 

  181. Nakazawa G, Finn AV, Virmani R. Vascular pathology of drug-eluting stents. Herz 2007;32:274–80.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 1485 Hoyt Ave W, Saint Paul, MN, 55108

    Daniel C. Sigg & Ayala Hezi-Yamit

Authors
  1. Daniel C. Sigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayala Hezi-Yamit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel C. Sigg .

Editor information

Editors and Affiliations

  1. Dept. Surgery, University of Minnesota, Delaware St. SE., 420, Minneapolis, 55455, U.S.A.

    Paul A. Iaizzo

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Sigg, D.C., Hezi-Yamit, A. (2009). Cardiac and Vascular Receptors and Signal Transduction. In: Iaizzo, P. (eds) Handbook of Cardiac Anatomy, Physiology, and Devices. Humana Press. https://doi.org/10.1007/978-1-60327-372-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-372-5_13

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-371-8

  • Online ISBN: 978-1-60327-372-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation