PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of worldjcardioLink to Publisher's site
 
World J Cardiol. 2009 December 31; 1(1): 23–25.
Published online 2009 December 31. doi:  10.4330/wjc.v1.i1.23
PMCID: PMC2999037

Prostate-specific antigen kallikrein and the heart

Abstract

Currently, there is growing interest regarding prostate-specific antigen (PSA) and the cardiovascular system. Increased PSA serum levels have been reported after prolonged cardiopulmonary resuscitation, cardiac surgery, extracorporeal cardiopulmonary bypass, acute myocardial infarction (AMI) and coronary artery stenting. The possible role of PSA in cardiac events has been questioned due to the finding of PSA decrease during AMI and by the correlation of variation in PSA levels with coronary lesions and occurrence of major adverse cardiac events. Complexed PSA forms and uncomplexed PSA forms are observed in the bloodstream but the increasing formation of irreversible bound PSA seems to be a crucial finding during AMI. Large studies need to be carried out to confirm these preliminary results and to elucidate unclear aspects. These findings present many potential directions for future research including the role of uncomplexed forms of PSA, the possible distribution of PSA in the heart, the relative expression levels in heart disease states, the mode of expression regulation and other potential specific substrates. The journey of PSA investigation could be longer than initially expected.

Keywords: Acute myocardial infarction, Cardiovascular system, Complexed prostate-specific antigen forms, uncomplexed prostate-specific antigen forms, Prostate-specific antigen kallikrein

Currently, a growing interest has been directed towards prostate-specific antigen kallikrein (PSA) and the cardiovascular system[1]. Increased PSA serum levels have been demonstrated after prolonged cardiopulmonary resuscitation[2,3], cardiac surgery[4], extracorporeal cardiopulmonary bypass[5-8], acute myocardial infarction (AMI)[9-15] and coronary artery stenting[16]. However, the possible role of PSA in cardiac events has been questioned due to the finding of PSA decrease during AMI and by the correlation of variation in PSA levels with coronary lesions and occurrence of major adverse cardiac events[17,18]. Recently, a decrease in PSA was also reported in a patient with coronary spasm and without significant coronary stenoses[19]. PSA is a 33 kDa single chain glycoprotein that was first identified in seminal plasma[20] and was subsequently isolated from prostate tissue[21,22]. It has been identified as a member of the human kallikrein family (hK3) of serine proteases[1,23-26] and was initially considered only as a marker for the detection of prostate cancer[27]. Other malignant and non-malignant, non-prostatic and non-cardiovascular diseases[27-32] are also associated with increased PSA serum levels and the PSA unspecificity to prostate, semen, and gender has been demonstrated[1,33-35]. Recently, attention has been focused on PSA as a ubiquitous protein by the finding of PSA in neuronal cells[35].

The inactive precursor form of PSA, proPSA, is converted rapidly to active PSA by hK2 and other proteases also seem to have a role in the formation of active PSA[1,36]. PSA expression has been shown to be primarily regulated by steroid hormones through androgen receptor-mediated transcription[27,35,37-42]. Two forms of PSA are observed in the bloodstream: complexed PSA forms and uncomplexed (free) PSA forms. Irreversible PSA complexes are formed with serum protease inhibitors and other acute-phase proteins[43-48]. Measurements of PSA levels are more reliable if interpreted in combination with information about C-reactive protein (CRP)[4]. The levels of increased bound PSA seem to have a significant correlation with high-sensitivity CRP and to a 14-d follow-up, with the occurrence of heart failure[48].

A higher occurrence of major adverse cardiac events after AMI and the finding of more frequent and more severe coronary lesions have been reported with elevation of PSA during AMI[1,15,17,48]. PSA in serum has been considered to be a biologically active factor[1,49], but the increasing formation of irreversible bound PSA seems to be a crucial finding during AMI[48]. Large studies need to be carried out to confirm these preliminary results and to elucidate unclear aspects. These findings present many potential directions for future research including the role of uncomplexed forms of PSA, the possible distribution of PSA in the heart, the relative expression levels in heart disease states, the mode of expression regulation and other potential specific substrates. The journey of PSA investigation could be longer than expected[1].

Footnotes

Peer reviewer: Alberto Dominguez-Rodriguez, MD, PhD, FESC, Department of Cardiology, University Hospital of Canarias, Ofras/n La Cuesta, La Laguna, E-38320, Tenerife, Spain

S- Editor Wang JL L- Editor Lutze M E- Editor Zheng XM

References

1. Patanè S, Marte F. Prostate-specific antigen kallikrein: from prostate cancer to cardiovascular system. Eur Heart J. 2009;30:1169–1170. [PubMed]
2. Koller-Strametz J, Fritzer M, Gwechenberger M, Geppert A, Heinz G, Haumer M, Koreny M, Maurer G, Siostrzonek P. Elevation of prostate-specific markers after cardiopulmonary resuscitation. Circulation. 2000;102:290–293. [PubMed]
3. Berent R, Auer J, Porodko M, Lamm G, Weber T, Wimmer E, Seier J, Aspöck G, Eber B. Influence of cardiopulmonary resuscitation on levels of tumour markers. Eur J Cancer Care (Engl) 2006;15:252–256. [PubMed]
4. Mahfouz RA, Cortas NK, Ibrahim G, Khalife S, Daher RT. Variations in prostate-specific antigen free/total ratio in acute stress. Scand J Clin Lab Invest. 2008;68:624–627. [PubMed]
5. Hagood PG, Parra RO, Rauscher JA. Nontraumatic elevation of prostate specific antigen following cardiac surgery and extracorporeal cardiopulmonary bypass. J Urol. 1994;152:2043–2045. [PubMed]
6. Parlaktas BS, Naseri E, Uluocak N, Elalmis AO, Erdemir F, Etikan I. Comparison of the effects of on-pump versus off-pump coronary artery bypass surgery on serum prostate-specific antigen levels. Int J Urol. 2006;13:234–237. [PubMed]
7. Netto Júnior NR, Lima ML, Guedes MA, Patino LL, de Oliveira JB. Elevation of prostate specific antigen in cardiac surgery with extracorporeal cardiopulmonary circulation. J Urol. 1998;159:875–877. [PubMed]
8. Guvel S, Turkoz R, Egilmez T, Kilinc F, Yaycioglu O, Atalay H, Ozkardes H. Does ischemia-induced prostate damage during cardiac surgery involving cardiopulmonary bypass cause bladder outlet obstruction? Urol Int. 2005;74:337–340. [PubMed]
9. Koreny M, Koller-Strametz J, Geppert A, Delle Karth G, Heinz G, Maurer G, Siostrzonek P. Elevation of prostatic markers following cardiogenic shock. Intensive Care Med. 2001;27:447. [PubMed]
10. Crook M, Preston K, Lancaster I. Serum prostatic specific-antigen concentrations in acute myocardial infarction. Clin Chem. 1997;43:1670. [PubMed]
11. Patanè S, Marte F. Paroxysmal ventricular tachycardia and paroxysmal atrial fibrillation associated with subclinical hyperthyroidism, chronic renal failure and elevation of prostate-specific antigen during acute myocardial infarction. Int J Cardiol. 2008:Epub ahead of print. [PubMed]
12. Patanè S, Marte F, Di Bella G, Ciccarello G. Changing axis deviation and elevation of prostate-specific antigen during acute myocardial infarction. Int J Cardiol. 2009;135:e4–e5. [PubMed]
13. Patanè S, Marte F, Di Bella G, Ciccarello G. Changing axis deviation, paroxysmal atrial fibrillation and elevation of prostate-specific antigen during acute myocardial infarction. Int J Cardiol. 2009;137:e37–e40. [PubMed]
14. Patanè S, Marte F. Paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of prostate-specific antigen after TURP. Int J Cardiol. 2008:Epub ahead of print. [PubMed]
15. Patanè S, Marte F, Sturiale M, Grassi R, Patanè F. Significant coronary artery disease associated with coronary artery aneurysm and elevation of prostate-specific antigen during acute myocardial infarction. Int J Cardiol. 2009:Epub ahead of print. [PubMed]
16. Ozcan T, Bozlu M, Muslu N, Gozukara KH, Seyis S, Akcay B. Elevation of the serum total and free prostate specific antigen levels after stent implantation in patients with coronary artery disease. Swiss Med Wkly. 2009;139:672–675. [PubMed]
17. Patanè S, Marte F. Prostate-specific antigen and acute myocardial infarction: A possible new intriguing scenario. Int J Cardiol. 2009;134:e147–e149. [PubMed]
18. Patanè S, Marte F. Prostate-specific antigen kallikrein and acute myocardial infarction: Where we are. Where are we going? Int J Cardiol. 2009:Epub ahead of print. [PubMed]
19. Patanè S, Marte F, Sturiale M, Dattilo G. ST-segment elevation and diminution of prostate-specific antigen in a patient with coronary spasm and without significant coronary stenoses. Int J Cardiol. 2009:Epub ahead of print. [PubMed]
20. Hara M, Koyanagi Y, Inoue T, Fukuyama T. [Some physico-chemical characteristics of " -seminoprotein", an antigenic component specific for human seminal plasma. Forensic immunological study of body fluids and secretion. VII] Nihon Hoigaku Zasshi. 1971;25:322–324. [PubMed]
21. Wang MC, Valenzuela LA, Murphy GP, Chu TM. Purification of a human prostate specific antigen. Invest Urol. 1979;17:159–163. [PubMed]
22. Nash AF, Melezinek I. The role of prostate specific antigen measurement in the detection and management of prostate cancer. Endocr Relat Cancer. 2000;7:37–51. [PubMed]
23. Lilja H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest. 1985;76:1899–1903. [PMC free article] [PubMed]
24. Watt KW, Lee PJ, M'Timkulu T, Chan WP, Loor R. Human prostate-specific antigen: structural and functional similarity with serine proteases. Proc Natl Acad Sci USA. 1986;83:3166–3170. [PubMed]
25. Lundwall A, Lilja H. Molecular cloning of human prostate specific antigen cDNA. FEBS Lett. 1987;214:317–322. [PubMed]
26. Schaller J, Akiyama K, Tsuda R, Hara M, Marti T, Rickli EE. Isolation, characterization and amino-acid sequence of gamma-seminoprotein, a glycoprotein from human seminal plasma. Eur J Biochem. 1987;170:111–120. [PubMed]
27. Graves HC. Nonprostatic sources of prostate-specific antigen: a steroid hormone-dependent phenomenon? Clin Chem. 1995;41:7–9. [PubMed]
28. Oesterling JE. Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145:907–923. [PubMed]
29. Schifman RB, Ahmann FR, Elvick A, Ahmann M, Coulis K, Brawer MK. Analytical and physiological characteristics of prostate-specific antigen and prostatic acid phosphatase in serum compared. Clin Chem. 1987;33:2086–2088. [PubMed]
30. Kiran PR. Markedly raised serum prostate specific antigen levels. Prostatic infarction rather than malignancy? Aust Fam Physician. 2001;30:458–460. [PubMed]
31. Yu H, Diamandis EP. Prostate-specific antigen in milk of lactating women. Clin Chem. 1995;41:54–58. [PubMed]
32. Yu H, Diamandis EP, Sutherland DJ. Immunoreactive prostate-specific antigen levels in female and male breast tumors and its association with steroid hormone receptors and patient age. Clin Biochem. 1994;27:75–79. [PubMed]
33. Olsson AY, Bjartell A, Lilja H, Lundwall A. Expression of prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) in ileum and other extraprostatic tissues. Int J Cancer. 2005;113:290–297. [PubMed]
34. Stephan C, Jung K, Diamandis EP, Rittenhouse HG, Lein M, Loening SA. Prostate-specific antigen, its molecular forms, and other kallikrein markers for detection of prostate cancer. Urology. 2002;59:2–8. [PubMed]
35. Stone JG, Rolston RK, Ueda M, Lee HG, Richardson SL, Castellani RJ, Perry G, Smith MA. Evidence for the Novel Expression of Human Kallikrein-related Peptidase 3, Prostate-Specific Antigen, in the Brain. Int J Clin Exp Pathol. 2009;2:267–274. [PMC free article] [PubMed]
36. Rittenhouse HG, Finlay JA, Mikolajczyk SD, Partin AW. Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci. 1998;35:275–368. [PubMed]
37. Shan JD, Porvari K, Ruokonen M, Karhu A, Launonen V, Hedberg P, Oikarinen J, Vihko P. Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein. Endocrinology. 1997;138:3764–3770. [PubMed]
38. Kim J, Coetzee GA. Prostate specific antigen gene regulation by androgen receptor. J Cell Biochem. 2004;93:233–241. [PubMed]
39. Kuriyama M, Wang MC, Lee CI, Papsidero LD, Killian CS, Inaji H, Slack NH, Nishiura T, Murphy GP, Chu TM. Use of human prostate-specific antigen in monitoring prostate cancer. Cancer Res. 1981;41:3874–3876. [PubMed]
40. Ercole CJ, Lange PH, Mathisen M, Chiou RK, Reddy PK, Vessella RL. Prostatic specific antigen and prostatic acid phosphatase in the monitoring and staging of patients with prostatic cancer. J Urol. 1987;138:1181–1184. [PubMed]
41. Murtha P, Tindall DJ, Young CY. Androgen induction of a human prostate-specific kallikrein, hKLK2: characterization of an androgen response element in the 5' promoter region of the gene. Biochemistry. 1993;32:6459–6464. [PubMed]
42. Luke MC, Coffey DS. Human androgen receptor binding to the androgen response element of prostate specific antigen. J Androl. 1994;15:41–51. [PubMed]
43. Zhou AM, Tewari PC, Bluestein BI, Caldwell GW, Larsen FL. Multiple forms of prostate-specific antigen in serum: differences in immunorecognition by monoclonal and polyclonal assays. Clin Chem. 1993;39:2483–2491. [PubMed]
44. Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate-specific antigen and alpha 1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res. 1991;51:222–226. [PubMed]
45. McConnell DJ. Inhibitors of kallikrein in human plasma. J Clin Invest. 1972;51:1611–1623. [PMC free article] [PubMed]
46. Lilja H, Christensson A, Dahlén U, Matikainen MT, Nilsson O, Pettersson K, Lövgren T. Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin. Clin Chem. 1991;37:1618–1625. [PubMed]
47. Becker C, Lilja H. Individual prostate-specific antigen (PSA) forms as prostate tumor markers. Clin Chim Acta. 1997;257:117–132. [PubMed]
48. Patanè S, Marte F, Sturiale M. Prostate-specific antigen kallikrein complexes and acute myocardial infarction. Int J Cardiol. 2009:Epub ahead of print. [PubMed]
49. Oremek GM, Seiffert UB. Physical activity releases prostate-specific antigen (PSA) from the prostate gland into blood and increases serum PSA concentrations. Clin Chem. 1996;42:691–695. [PubMed]

Articles from World Journal of Cardiology are provided here courtesy of Baishideng Publishing Group Inc