Frontiers in Physiology (Oct 2018)
Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation—Implications for Abdominal Aortic Aneurysm Susceptibility
- Markus U. Wagenhäuser,
- Markus U. Wagenhäuser,
- Markus U. Wagenhäuser,
- Isabel N. Schellinger,
- Isabel N. Schellinger,
- Isabel N. Schellinger,
- Takuya Yoshino,
- Takuya Yoshino,
- Kensuke Toyama,
- Kensuke Toyama,
- Yosuke Kayama,
- Yosuke Kayama,
- Alicia Deng,
- Alicia Deng,
- Sabina P. Guenther,
- Sabina P. Guenther,
- Anne Petzold,
- Joscha Mulorz,
- Joscha Mulorz,
- Joscha Mulorz,
- Pireyatharsheny Mulorz,
- Pireyatharsheny Mulorz,
- Gerd Hasenfuß,
- Wiebke Ibing,
- Margitta Elvers,
- Andreas Schuster,
- Andreas Schuster,
- Andreas Schuster,
- Anand K. Ramasubramanian,
- Matti Adam,
- Matti Adam,
- Hubert Schelzig,
- Joshua M. Spin,
- Joshua M. Spin,
- Uwe Raaz,
- Uwe Raaz,
- Philip S. Tsao,
- Philip S. Tsao
Affiliations
- Markus U. Wagenhäuser
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Markus U. Wagenhäuser
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Markus U. Wagenhäuser
- Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
- Isabel N. Schellinger
- Molecular and Translational Vascular Medicine, Department of Cardiology and Pneumology, Heart Center at the University Medical Center Göttingen, Göttingen, Germany
- Isabel N. Schellinger
- German Center for Cardiovascular Research e.V., Göttingen, Germany
- Isabel N. Schellinger
- Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany
- Takuya Yoshino
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Takuya Yoshino
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Kensuke Toyama
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Kensuke Toyama
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Yosuke Kayama
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Yosuke Kayama
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Alicia Deng
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Alicia Deng
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Sabina P. Guenther
- Department of Cardiac Surgery, University Hospital Munich, Ludwig-Maximilian-University, Munich, Germany
- Sabina P. Guenther
- Department of Surgery, University of California, San Francisco, San Francisco, CA, United States
- Anne Petzold
- Molecular and Translational Vascular Medicine, Department of Cardiology and Pneumology, Heart Center at the University Medical Center Göttingen, Göttingen, Germany
- Joscha Mulorz
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Joscha Mulorz
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Joscha Mulorz
- Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
- Pireyatharsheny Mulorz
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Pireyatharsheny Mulorz
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Gerd Hasenfuß
- German Center for Cardiovascular Research e.V., Göttingen, Germany
- Wiebke Ibing
- Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
- Margitta Elvers
- Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
- Andreas Schuster
- Molecular and Translational Vascular Medicine, Department of Cardiology and Pneumology, Heart Center at the University Medical Center Göttingen, Göttingen, Germany
- Andreas Schuster
- German Center for Cardiovascular Research e.V., Göttingen, Germany
- Andreas Schuster
- Department of Cardiology, Royal North Shore Hospital, The Kolling Institute, Northern Clinical School, University of Sydney, Sydney, NSW, Australia
- Anand K. Ramasubramanian
- 0Department of Biomedical, Chemical and Materials Engineering, San Jose State University, San Jose, CA, United States
- Matti Adam
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Matti Adam
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Hubert Schelzig
- Department of Vascular and Endovascular Surgery, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
- Joshua M. Spin
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Joshua M. Spin
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- Uwe Raaz
- Molecular and Translational Vascular Medicine, Department of Cardiology and Pneumology, Heart Center at the University Medical Center Göttingen, Göttingen, Germany
- Uwe Raaz
- German Center for Cardiovascular Research e.V., Göttingen, Germany
- Philip S. Tsao
- Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States
- Philip S. Tsao
- VA Palo Alto Health Care System, Palo Alto, CA, United States
- DOI
- https://doi.org/10.3389/fphys.2018.01459
- Journal volume & issue
-
Vol. 9
Abstract
Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness.Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed.Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening.Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.
Keywords
