Author + information
- Received February 20, 2018
- Revision received June 4, 2018
- Accepted June 10, 2018
- Published online August 6, 2018.
- Tim De Meyer, PhDa,∗ (, )@ugent@CNIC_CARDIO@uhasselt,
- Tim Nawrot, PhDb,
- Sofie Bekaert, PhDc,
- Marc L. De Buyzere, BScd,
- Ernst R. Rietzschel, MD, PhDd and
- Vicente Andrés, PhDe,f
- aDepartment of Data Analysis and Mathematical Modelling, Ghent University, Belgium
- bCentre for Environmental Sciences, Hasselt University, Hasselt, Belgium
- cBimetra Clinical Research Center, Ghent University Hospital, Ghent, Belgium
- dDepartment of Cardiovascular Diseases, Ghent University, Ghent, Belgium
- eCentro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
- fCIBER de Enfermedades Cardiovasculares (CIBER-CV), Madrid, Spain
- ↵∗Address for correspondence:
Dr. Tim De Meyer, Department of Data Analysis and Mathematical Modelling, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B9000 Ghent, Belgium.
Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore remains uncertain whether telomere shortening is a cause of aCVD or merely a consequence. The authors argue that elucidating the mechanistic foundation of these findings is essential for any possible translation of telomere biology to the clinic. Here, they critically evaluate evidence for causality in animal models and human studies, and review popular hypotheses and discuss their clinical implications. The authors identify 4 key questions that any successful mechanistic theory should address, and they discuss how atherosclerosis-associated local telomere attrition may provide the answers.
Funding provided by the Spanish Ministerio de Economía, Industria y Competitividad and the Pro-CNIC Foundation, and a Severo Ochoa Center of Excellence (award SEV-2015-0505) in support of CNIC. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 20, 2018.
- Revision received June 4, 2018.
- Accepted June 10, 2018.
- 2018 American College of Cardiology Foundation
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