Original Article

Subject Category: Experimental Medicine

Citation: Cell Death and Disease (2012) 3, e424; doi:10.1038/cddis.2012.162
Published online 15 November 2012

Apoptosis and necrosis: two different outcomes of cigarette smoke condensate-induced endothelial cell death

B Messner1, S Frotschnig2, A Steinacher-Nigisch1, B Winter1, E Eichmair1, J Gebetsberger2,3, S Schwaiger4, C Ploner5, G Laufer1 and D Bernhard1

  1. 1Cardiac Surgery Research Laboratory, Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, Vienna 1090, Austria
  2. 2Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Innsbruck Medical University, Innrain 66, Innsbruck A-6020, Austria
  3. 3Division of Genomics and RNomics, Innsbruck Biocenter, Innsbruck Medical University, Fritz Pregel Street 3, Innsbruck 6020, Austria
  4. 4Department of Pharmacognosy, Institute of Pharmacy, University of Innsbruck, Josef-Moeller-Haus, Innrain 52c, Innsbruck A-6020, Austria
  5. 5Department of Operative Medicine, Plastic, Reconstructive and Aesthetic Surgery Innsbruck, Innsbruck Medical University, Anichstrasse 35, Innsbruck A-6020, Austria

Correspondence: B Messner, Cardiac Surgery Research Laboratories, Department of Surgery, Medical University of Vienna, AKH, Ebene 8 G09/07, Währinger Gürtel 18-20, Vienna A-1090, Austria. Tel: +43 1 40400 6949; Fax: +43 1 40400 6782; E-mail: Barbara.Messner@meduniwien.ac.at

Received 16 July 2012; Revised 28 August 2012; Accepted 4 September 2012

Edited by A Stephanou



Cigarette smoking is one of the most important and preventable risk factors for atherosclerosis. However, because of the complex composition of cigarette smoke, the detailed pathophysiological mechanisms are not fully understood. Based on controversial reports on the pro-atherogenic activity of cigarette smoke condensate, also called tar fraction (CSC), we decided to analyse the effects of CSC on the viability of endothelial cells in vitro. The results of this study show that low concentrations of the hydrophobic tar fraction induces DNA damage resulting in a P53-dependent and BCL-XL-inhibitable death cascade. Western blot analyses showed that this cascade is caspase-independent and immunofluorescence analysis have shown that the apoptotic death signalling is mediated by the release of apoptosis-inducing factor. Higher CSC concentrations also induce apoptotic-like signalling but the signalling cascade is then redirected to necrosis. Despite the fact that CSC induces a profound increase in cellular reactive oxygen species production, antioxidants exhibit only a minimal cell death protective effect. Our data indicates that not only hydrophilic constituents of cigarette smoke extract, but also CSC is harmful to endothelial cells. The mode and the outcome of CSC-induced cell death signalling are highly concentration dependent: lower concentrations induce caspase-independent apoptosis-like cell death, whereas incubation with higher concentrations interrupts apoptotic signalling and induces necrosis.


atherosclerosis; cigarette smoke condensate; apoptosis; necrosis; P53; BCL-XL


CSC, cigarette smoke condensate; CSE, cigarette smoke extract; AIF, apoptosis inducing factor; LC3, microtubule associated protein light chain 3; LDH, lactate dehydrogenase; ATP, adenosine triphosphate; ROS, reactive oxygen species; 3-MA, 3-methyladenine; NAC, N-acetylcysteine; DHR, dihydrorhodamine