Expression of NTPDase1 and caveolins in human cardiovascular disease
- 133 Downloads
Pathological circumstances like inflammation or ischemic insult facilitate the release of adenine nucleotides from several types of cells. These extracellular nucleotides are rapidly converted to adenosine by ectonucleotidases, mainly ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1/CD39) and CD73. NTPDase1/CD39 can interact with caveolins, structural proteins of signal-transducing microdomains termed caveolae. Caveolins are thought to have physiological roles in heart ageing and cardiac diseases. The aim of this study was to investigate the expression of NTPDase1 together with caveolins in chronic human cardiovascular diseases and elucidate their role in human heart. The HPLC analysis showed significant increase in ATPase activity in pathological samples from patients with ischemic heart disease. Immunostaining also showed alterations in the expression and distribution of NTPDase1. Caveolin-1 and caveolin-2 expression was much alike in control and pathological cases, while expression of caveolin-3 was lower in pathological samples. Changes in the expression of NTPDase1 and caveolins seem to be independent of human cardiovascular disease.
KeywordsNTPDase1 Caveolins HPLC Ultracryo immunohistochemistry Enzyme histochemistry
This work was supported by Hungarian grants ETT 480/2003, ETT472/2003, OTKA M036314, OTKA T037457 and OTKA T34722. The authors thank Mária Baranyi, Éva Szénássy, Judit Őszi for providing technical expertise and assistance and Margit Kutasi, Katalin Lőcsey for excellent technical assistance.
- Capozza F, Combs TP, Cohen AW, Cho YR, Park SY, Schubert W, Williams TM, Brasaemle DL, Jelicks LA, Scherer PE, Kim JK, Lisanti MP (2005) Caveolin-3 (−/−) Knockout Mice Show Increased Adiposity and Whole-Body Insulin Resistance, with Ligand-Induced Insulin Receptor Instability in Skeletal Muscle. Am J Physiol Cell Physiol DOI:10.1152/ajpcell.00489.2004Google Scholar
- Fazekas L, Horkay F, Kékesi V, Barát E, Huszár É, Fazekas R, Szabó T, Juhász-Nagy S, Naszlady A (1998) Elevation of adenosine and inosine concentrations in the pericardial fluid of human patients with coronary artery disease. Cardiol Hung 27:7–10Google Scholar
- Machida T, Heerdt PM, Reid AC, Schaefer U, Silver RB, Broekman MJ, Marcus AJ, Levi R (2005) E-NTPDase1/CD39, localized in neurons of human and porcine heart, modulates ATP-induced norepinephrine exocytosis. J Pharmacol Exp Ther DOI:10.1124/jpet.104.081240Google Scholar
- Pinsky DJ, Broekman MJ, Peschon JJ, Stocking KL, Fujita T, Ramasamy R, Connolly ES Jr, Huang J, Kiss S, Zhang Y, Choudhri TF, McTaggart RA, Liao H, Drosopoulos JH, Price VL, Marcus AJ, Maliszewski CR (2002) Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic brain. J Clin Invest 109:1031–1040PubMedCrossRefGoogle Scholar
- Ratajczak P, Oliviero P, Marotte F, Kolar F, Ostadal B, Samuel JL (2005) Expression and localisation of caveolins during postnatal development in rat heart. Implication of thyroid hormone. J Appl Physiol DOI 10.1152/japplphysiol.01292.2004Google Scholar
- Sevigny J, Sundberg C, Braun N, Guckelberger O, Csizmadia E, Qawi I, Imai M, Zimmermann H, Robson SC (2002) Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation. Blood 99:2801–2809PubMedCrossRefGoogle Scholar